Tag Archives: Alzheimer

China approves world’s first Alzheimer’s drug in 20 years

Inspired by the low occurrence of the disease among those who consume seaweed, the world’s first drug for the treatment of Alzheimer’s in almost two decades just got the green light by the Chinese government, opening the door to a treatment to reverse the condition.

Credit Wikipedia Commons

The drug was approved for the treatment of “mild to moderate Alzheimer disease and improving brain function,” according to China’s National Medical Products Administration. It will now take a few more years to actually start producing the drug.

The Chinese research team, led by Dr. Geng Meiyu at the Chinese Academy of Sciences’ Shanghai Institute of Materia Medica, started looking into possible connections and, in 1997, identified a unique sugar in seaweed which might play an important role in the phenomenon.

They did not anticipate that developing the idea into an effective drug would take them more than two decades. “I did feel lonely sometimes because others were all developing small molecule medicines. Using sugar (with large molecular structure) was unprecedented,” Geng said, in an interview last year.

Today there’s no cure for Alzheimer’s. As brain cells degenerate, symptoms progress from repeated words, depression, getting lost in familiar neighborhoods, to forgetting the faces of family members. There will be 150 million Alzheimer’s patients around the world by 2050, according to the World Health Organization.

The decline in brain function caused by Alzheimer’s can be divided into seven stages, and the new drug has been proven effective on conditions up to stage 4, which includes difficulty to add simple numbers, recall what was eaten for breakfast, pay bills or remember details about life histories.

Over the past two decades, pharmaceutical companies have invested hundreds of billions and brought more than 320 candidate drugs to a clinical trial. Only five were approved for clinical use to relieve symptoms, and none could stop the brain cells from withering away.

Geng’s team published a paper announcing a major discovery in September. They had found that Oligomannat was, in fact, a multitasking agent. It not only reduces the formation of a protein harmful to neurons but also regulates the bacterium colonies in human intestines to reduce the risk of brain inflammation.

The approval for Oligomannate was not unconditional. Green Valley, the Shanghai-based pharmaceutical company which is to produce the drug, was “required to continue research on pharmacological mechanisms and long-term evaluation on safety and effectiveness,” according to the approval document.

In a clinical trial on more than 800 volunteers, the new drug was shown to improve cognitive performance by an average of 2.54 points in a standard test with scores from 0 to 70, in which patients scoring 16 points or more could be diagnosed with Alzheimer’s.

Lu Songtao, president of Green Valley, said the drug was in production at a plant in Liaoning province, northeast China, and would be available to the domestic market before the end of the year. Construction, to US standards, would also soon begin on a new factory in Shanghai.

“If the construction can be finished within three years, this factory will be able to satisfy the demand for two million patients every year,” Lu said. “Hopefully the drug will become available in global markets at around the same time,” he added.

Handstand.

Healthy lifestyles can offset the genetic risk of dementia by 32%

Lifestyle choices can help reduce an individual’s genetic risk of dementia, a new paper reports.

Handstand.

Image credits Matan Ray Vizel.

New research led by researchers from the University of Exeter found that people with a high genetic risk of dementia has a 32% lower risk of developing the syndrome if they followed a healthy lifestyle, compared with their counterparts who had an unhealthy lifestyle. Participants with high genetic risk and an unfavourable lifestyle were almost three times more likely to develop dementia than those with a low genetic risk and a favourable lifestyle (a 2.83 increased occurrence of dementia from any cause).

Do good, be good

“This research delivers a really important message that undermines a fatalistic view of dementia,” says co-lead author Dr. David Llewellyn, from the University of Exeter Medical School and the Alan Turing Institute.

“Some people believe it’s inevitable they’ll develop dementia because of their genetics. However it appears that you may be able to substantially reduce your dementia risk by living a healthy lifestyle.”

The team worked with data from 196,383 adults of European ancestry aged 60 and older from UK Biobank. Out of this sample, the team identified 1,769 cases of dementia over the follow-up period of eight years. They then grouped all participants into three groups: those with high, intermediate, and low genetic risk for dementia.

“Our findings are exciting as they show that we can take action to try to offset our genetic risk for dementia,” says Joint lead author Dr Elzbieta Kuzma. “Sticking to a healthy lifestyle was associated with a reduced risk of dementia, regardless of the genetic risk.”

In order to assess genetic risk for dementia, the team looked at previous research to identify all currently-known genetic risk factors for Alzheimer’s disease. Each genetic risk factor was weighted according to the strength of its association with the disease.

To assess lifestyle, the team defined three groups based on their self-reported diet, physical activity, smoking, and alcohol consumption: favorable, intermediate, and unfavorable. People who didn’t currently smoke, engaged in regular physical activity, had a healthy diet, and only had moderate levels of alcohol intake were considered to be part of the ‘favorable’ group. A healthy lifestyle was associated with a reduced risk of dementia across all the genetic risk groups.

The paper “Association of Lifestyle and Genetic Risk With Incidence of Dementia” has been published in the journal JAMA

How to prevent dementia, according to new WHO guidelines

Dementia refers to the decline in mental ability that is severe enough to impair a person’s ability to perform everyday activities. It affects memory, thinking, orientation, comprehension, calculation, learning capacity, language, and judgement. Around 50 million people worldwide have dementia with Alzheimer’s disease as the most common type. And every year brings 10 million new cases, says the report recently released by the World Health Organization (WHO).

“In the next 30 years, the number of people with dementia is expected to triple,” said WHO Director-General Dr Tedros Adhanom Ghebreyesus. “We need to do everything we can to reduce our risk of dementia. The scientific evidence gathered for these guidelines confirms what we have suspected for some time, that what is good for our heart, is also good for our brain.”

Age is a risk factor so the older you are, the more likely you are to develop dementia. Certain genetic factors are involved with some more unusual forms of dementia — for the most part, dementia develops as a combination of genetic and “environmental” factors (i.e. smoking, lack of regular exercise). Although age is the top risk factor, “dementia is not a natural or inevitable consequence of aging,” the report says.

The report outlined what in WHO’s expert opinion think will and won’t help reduce the risk of dementia. So, if you want to save your brain, here are the do’s and don’ts from the new WHO guidelines for preventing dementia.

The DO’s

Exercise. The role of exercise is especially important. A physically active lifestyle is linked to brain health. A recent study of more than 1,600 people over age 65 found that those who spent more time sitting had the same risk of developing dementia as people who carry a genetic mutation that puts them at higher risk of Alzheimer’s. Weight loss could indirectly reduce the risk of dementia by improving a variety of metabolic factors linked with cognitive impairment and dementia (i.e. glucose tolerance, insulin sensitivity, blood pressure, oxidative stress, and inflammation).

Continue Learning. You’ve heard the saying: “use it or lose it.” Studies show that those who utilize their brains more by learning a new language or musical instrument, or furthering their education tend to have lower rates of dementia and problems with their thinking later in life.

Eat well. A healthy diet contains fruits, vegetables, legumes, nuts, and whole grains. In particular, committing to a Mediterranean diet (plant-based cooking, little meat and a heavy emphasis on olive oil) could help. The Mediterranean diet is the most extensively studied dietary approach, in general as well as in relation to cognitive function. Several systematic reviews of observational studies have concluded that high adherence to this diet is associated with decreased risk of mild cognitive impairment and Alzheimer’s Disease, but modest adherence is not.

Socialize. Socialization is important for all of us. Engaging with other people in social situations help patients suffering from Alzheimer’s disease and other forms of dementia and may even slow the progress of these conditions. The Lancet Commission on Dementia Prevention, Intervention, and Care identified social engagement as an intervention that could be used to prevent dementia

Lower Blood Pressure. Lowering blood pressure may help protect memory and thinking skills later in life. A large blood pressure study, called Systolic Blood Pressure Intervention Trial, or SPRINT, looked at over 9,000 people over the age of 50 years old and found that those who lowered their blood pressure to 120 (systolic blood pressure) were 19 percent less likely to develop cognitive impairment. Results were published in the Journal of the American Medical Association (JAMA).

The DON’TS

Don’t Smoke. There is strong evidence that smoking is associated with an increased risk of dementia. The toxins in cigarette smoke increase oxidative stress and inflammation, which have both been linked to developing of Alzheimer’s disease. Tobacco cessation is associated with reduced depression, anxiety and stress, and improved mood and quality of life compared with continuing to smoke.

Don’t drink too much. Excessive alcohol consumption leads to numerous health problems such as liver damage, stomach issues, impaired cognitive function, and more. If alcoholic beverages are consumed in large quantities over a relatively short period of times, most health problems can be cured relatively easily using special treatment and by quitting drinking. However, if one abuses alcohol throughout many years, this doesn’t only lead to liver cirrhosis, but also a condition called alcoholic dementia. There is extensive evidence on excessive alcohol as a risk factor for dementia and cognitive decline.

Don’t waste money on supplements. There is currently no evidence to show that taking supplements (i.e. B vitamins, antioxidants, omega-3 ginkgo) reduces the risk of cognitive decline and dementia. In fact, scientific evidence shows that in high doses these supplements may be harmful.

These potentially modifiable risk factors mean that prevention of dementia is possible through a public health approach, including key interventions that delay or slow cognitive decline or dementia. Much of the WHO’s advice is common sense and aligns with what the US National Institute on Aging advises.

Poor sleep linked to increased risk of Alzheimer’s disease

Researchers have discovered that daytime sleepiness might cause brain build-ups leading to Alzheimer’s disease (AD).

Via Pixabay/gracic

Elderly people feeling drowsy during the day due to poor sleep or waking up in the night had a greater build-up in their brain of amyloid plaques which consume the brain, kill cells, and eventually lead to total memory loss. And this makes sense: recent studies have shown that while the brain sleeps, it clears away deposits of amyloid.

Even though previous research showed a correlation between sleepiness and AD, scientists wondered if the accumulation of amyloid plaques in the patients’ brains caused sleep problems or if it was the other way around.

Now, a team led by Mayo Clinic’s Prashanthi Vemuri has cast light on the subject: sleep itself seems to be causing the plaque accumulation that triggers the neurodegenerative disease.

“This study is the first in humans to demonstrate a predictive association between a measure of sleep disturbance at baseline and change in an AD [Alzheimer’s disease] biomarker across multiple points,” Joseph R. Winer and Bryce A. Mander, of the University of California, wrote in an editorial published with the study in the Journal of the American Medical Association.

The research team studied 283 people aged 70 or older without dementia from the center’s Study of Aging. Each participant completed surveys that assessed their general sleepiness and had at least two consecutive imaging scans of their brains from 2009 to 2016. The scans monitored the difference in amyloid plaque quantity between two scans in different regions of the brain.

Researchers discovered that 63 participants (22.3%) had excessive daytime sleepiness, and this was associated with increased amyloid plaque accumulation in susceptible regions of the brain.

“We found that daytime sleepiness was causing more deposition of amyloid in people who are already amyloid positive, so it was influencing the rate of deposition over time,” Dr. Vermuri said.

Although the study seems to establish causation between sleep patterns and amyloid accumulation, the team still has no definitive answer to why and how sleep has this effect.

However, experts consider this study a breakthrough, believing the findings underline the importance of good sleep for preserving brain health.

“This study and others present evidence that poor sleep quality may be an early warning sign of AD-related processes,” Winer and Mander wrote. “Although a better understanding of the role of sleep in the AD cascade could soon lead to effective sleep-based therapies, at present, maintaining healthy sleep and treating clinical sleep disorders must be a current priority for mental health in older adults.:

Scientists develop new Alzheimer’s blood test for early signs

Scientists from Australia and Japan have invented a blood test that assesses the levels of beta-amyloid build-up in the brain. Beta-amyloids are amino acids crucially involved in Alzheimer’s disease.

Source: Wikipedia

The battle against Alzheimer’s is a hard one

Accumulation of beta-amyloid decreases neuronal activity in large areas of the brain. However, beta-amyloid builds up in the brain of an Alzheimer’s patient decades before any clinical signs — such as cognitive problems and loss of memory — show up. This means that in theory, detecting beta-amyloid could enable physicians to detect Alzheimer’s before it actually sets in.

For decades, scientists have been trying to design a blood test, especially as current methods are expensive and cannot be used as screening methods on a large scale. Nowadays, doctors use positron emission tomography imaging (PET scans) or cerebrospinal fluid (CSF) analysis via spinal tap or lumbar puncture to diagnose the disease. That’s not only expensive, but also invasive, unpleasant, and time-consuming. Having a simple blood test could change all that.

However, designing a screening test for the disease has proven extremely difficult as relatively little beta-amyloid is found in the bloodstream, compared to how much lies in the brain. Most past studies have failed to find a correlation between the two but now for the first time, researchers believe they have finally cracked that problem.

Colin Masters, a professor of neuroscience at the Melbourne-based Florey Institute, who has spent 30 years researching an Alzheimer’s test, said mass spectrometry was more sensitive and accurate at detecting beta-amyloid levels than PET brain scans and lumbar punctures. He managed to successfully use this technique to detect beta-amyloid building up in the blood.

“By the time you hit 60 to 70 about 30% of the population are showing signs of this protein aggregating in their brain and that can be picked up now with this blood test,”  said Prof Masters.

Beta-amyloid structure.
Via: Wikipedia

The blood test, a new hope

A new, painless and more cost-effective Alzheimer’s test could help more people know if they are on the path of developing this condition. This could not only help detect Alzheimer’s quicker and more efficiently, but it could also help researchers ultimately find a cure — ensuring that future medical trials have numerous suitable participants, something which has proven challenging. Usually, present participants have late-stage Alzheimer’s that is treatment-resistant. It is extremely difficult to see if a kind of medicine is helping without having numerous early-stage patients enrolled in trials. If this simple blood test gets scientific approval, it might turn the odds in researchers’ favor.

“If a person knows they are on this pathway well before the onset of any cognitive impairment some would want to alter their lifestyles,” Prof Masters said.

The study included 121 people from Japan and 252 from Australia, both groups involving Alzheimer’s patients with normal brain function and mild cognitive impairment. Researchers found the amount of amyloid present in the blood correlated with the degree of cognitive impairment. Amyloid levels also correlated with findings in the same patients from classical diagnostic tools, PET scans, and CSF measures.

James Hendrix, director of Global Science Initiatives for the Alzheimer’s Association (the largest nonprofit funder of Alzheimer’s research), who was not involved in the new research, thinks that this is a truly important study.

“It is from a top research team. It is a decently large sample size. And most important, they are correlating their results to PET and CSF. That cross-validation to other techniques is great to see—we haven’t seen this before for a blood test in Alzheimer’s,” he said in a statement.

Neurofibrillary tangles in the Hippocampus of an old person with Alzheimer-related pathology.
Via: Wikipedia

 

“I can see in the future, five years from now, where people have a regular checkup every five years after age 55 or 60 to determine whether they are on the Alzheimer’s pathway or not,” hopes Prof Masters.

The paper was published Jan. 31 in the journal Nature.

Bill Gates invests $100 million to study and defeat Alzheimer’s

Say what you want about Gates as a businessman but as a philanthropist, he’s definitely putting his money where his mouth is. His latest enterprise is fighting Alzheimer’s disease, which affects 30 million people every year and kills almost 2 million.

A health revolution

Despite what you may see on the news, this is the best time to be alive. This isn’t saying that everything is peachy in the world — quite the opposite can be said in many areas of the planet — but it is, on average, better than at any point in human history. Thanks to continuous advancements in science, we’re living more than ever. In the developed world, at least, people routinely live to be 80 or even 90 years old. In other words, we’ve pretty much figured out how to make people live longer, though the practices aren’t yet implemented in most parts of the world. But now, it’s time for a new revolution: it’s not only about making people live longer, but it’s more about making sure that they make the most out of those extra years.

“In every part of the world, people are living longer than they used to,” Gates writes on his blog. “Thanks to scientific advancements, fewer people die young from heart disease, cancer, and infectious diseases. It’s no longer unusual for a person to live well into their 80s and beyond. My dad will celebrate his 92nd birthday in a couple weeks, a milestone that was practically unimaginable when he was born.”

“This fact—that people are living longer than ever before—should always be a wonderful thing. But what happens when it’s not?”

Gates was specifically referring to Alzheimer’s. The disease, which causes 60% to 70% of cases of dementia, devastates both those who have it and their loved ones. The most common early symptom is difficulty in remembering recent events, but as the disease progresses, symptoms become much stronger and harder to manage.

The causes of Alzheimer’s are poorly understood, but scientists have seen that the disease is tightly connected to aging. The damage that the disease does is also very difficult to quantify. However, the financial cost is easier to calculate. As Gates explains, Americans will spend $259 billion caring for those with Alzheimer’s and other dementias in 2017. Unless unforeseen advancements take place in future years, that figure will continue to grow.

“I first became interested in Alzheimer’s because of its costs—both emotional and economic—to families and healthcare systems. The financial burden of the disease is much easier to quantify. A person with Alzheimer’s or another form of dementia spends five times more every year out-of-pocket on healthcare than a senior without a neurodegenerative condition. Unlike those with many chronic diseases, people with Alzheimer’s incur long-term care costs as well as direct medical expenses. If you get the disease in your 60s or 70s, you might require expensive care for decades.”

Investing in a healthier future

In the case of Alzheimer’s, just like in most medical problems, hefty investments can not only improve the quality of life for people, but they can also save a lot of money. Gates believes that by investing $100 million, he will be saving mankind much more than that in the long run, in addition to making a positive impact for millions of people. So he’s investing $50 million in start-up ventures working in Alzheimer’s research, and another $50 million in the Dementia Discovery Fund — a fund that brings together NGOs, governments, and industries to provide much-needed investment in innovative therapies and treatment avenues for Alzheimer’s. The main objectives of this investment are:

  • Understanding how Alzheimer’s emerges and unfolds. The brain is a complex and complicated organ, every disease that affects it is bound to be complex itself.
  • Diagnosing Alzheimer’s sooner. There is no direct way to diagnose Alzheimer’s — except an autopsy. We need to better identify this disease if we want to treat it.
  • Finding more treatment approaches. Many drugs to treat Alzheimer’s exist, but they generally follow similar avenues. We need to diversify our approach, Gates says.
  • Making it easier for people to get involved in clinical trials. There’s a lot of research going on in the field, but it can sometimes take years to enroll patients for studies.
  • Using data in a better way. Every time a study is carried out, lots and lots of information are gathered, but sometimes, this data isn’t accessible or compiled for others to use.

“By improving in each of these areas, I think we can develop an intervention that drastically reduces the impact of Alzheimer’s. There are plenty of reasons to be optimistic about our chances: our understanding of the brain and the disease is advancing a great deal. We’re already making progress—but we need to do more,” Gates concludes.

Dolphins can also get Alzheimer’s, surprising new study finds

Humans aren’t unique in getting Alzheimer’s — Oxford researchers have found that dolphins can get both Alzheimer’s and Type 2 Diabetes. These diseases might be a consequence of longer lifespans.

At a first glance, few animals seem more different than humans and dolphins. We live on the ground, they live underwater. We have hands and feet, they have fins. But if you look a bit deeper, you start to see a lot of similarities. We’re both mammals with complex tight-knit social groups, we both use complex vocalizations, and we’re both quite intelligent. Now, researchers have found another aspect that strengthens that bond: degenerative disease.

Simon Lovestone, an old age psychiatrist from Oxford Health NHS Foundation Trust, carried out a review of previous studies to see how common it is for other animals to suffer from Alzheimer’s. He found no evidence of onset in any other species.

‘It is very rare to find signs of full-blown Alzheimer’s Disease in non-human brains,’ said Professor Lovestone, who also studies dementia for the National Institute for Health Research (NIHR). ‘This is the first time anyone has found such clear evidence of the protein plaques and tangles associated with Alzheimer’s Disease in the brain of a wild animal.’

Before Lovestone actually found evidence of Alzheimer’s in dolphins, he identified a potential predilection of the marine mammals towards the disease. Thankfully, he told the right people about it.

‘It was a moment of serendipity when I heard Simon give a talk about the possibility that dolphins might be predicted to get dementia, as our collaborators have previously worked with dolphins,’ said Professor Frank Gunn-Moore from the University of St Andrews.

Alzheimer’s “eats” from your brain. Image via Wikipedia.

Humans and dolphin have another, rather unusual, trait in common: we continue to live long after our fertility declines. Regardless of their overall lifespan, animals don’t tend to live long after their fertility declines. In a competitive environment, this makes a lot of sense: you can’t make more offspring, so your utility to the species is limited. But humans and dolphins are different. Both for men and women, fertility declines sharply after 40 years, but people can go on to live 100 and even more. A similar process happens to dolphins (and orcas).

In order to prove their theory, researchers analyzed the brains of dolphins washed ashore on the Spanish coast. They were specifically looking at ‘plaques’ of a protein called beta-amyloid in the brains of dolphins, as well as tangles of another protein called tau. These are the main signatures of Alzheimer’s disease, and both of them were identified in the washed dolphins. Researchers believe that the hormone called insulin is directly connected to this process. Insulin regulates levels of sugar in the blood and starts a complex cascade of chemical reactions which have a dramatic impact on the body. Mice studies, for instance, have shown that extreme calorie restriction affected insulin signaling, which in turn extended the lifespan of the mice by up to 300%. If this is the case in the cetaceans, then Alzheimer’s (and possibly diabetes) might be a result of living longer.

‘We think that in humans, the insulin signalling has evolved to work in a way similar to that artificially produced by giving a mouse very few calories’, says Professor Lovestone. ‘That has the effect of prolonging lifespan beyond the fertile years, but it also leaves us open to diabetes and Alzheimer’s Disease. Previous work shows that insulin resistance predicts the development of Alzheimer’s Disease in people, and people with diabetes are more likely to develop Alzheimer’s.’

‘But our study suggests that dolphins and orcas (who also have a long post fertility life span) are similar to humans in many ways; they have an insulin signalling system that makes them an interesting model of diabetes, and now we have shown that dolphin brains show signs of Alzheimer’s identical to those seen in people.’

Researchers still aren’t sure if dolphin Alzheimer’s manifests itself like in humans. Without studying dolphins in the wild, it’s impossible to say if they suffer from the same confusion and memory problems reported in Alzheimer’s patients. The team doesn’t advocate carrying out studies on captive dolphins.

However, this might also be important for developing new treatments for the disease. Treating it in the brain is very difficult early on, as there is little cerebral damage at this point, making it difficult to find a treatment target. But if the disease is connected to insulin signaling, then scientists could work on that, and develop a whole new avenue for Alzheimer’s treatment.

The full paper, ‘Alzheimer’s disease in humans and other animals: A consequence of postreproductive life span and longevity rather than aging‘, can be read in the journal Alzheimer’s & Dementia.

dementia

Scientists think they have a good drug target to prevent Alzheimer’s

dementia

Credit: Pixabay

Alzheimer’s disease is one of the most common neurodegenerative disorders, affecting 5.4 million Americans. It’s estimated that one in three seniors die of Alzheimer’s or some other form of dementia, and life’s not easy once the disease takes its toll either. To make matters worse, there’s no cure — only treatments that help stave off the inevitable. That’s why a team from Baylor College of Medicine, Texas Children’s Hospital and Johns Hopkins University School of Medicine, were more preoccupied with subduing early events that lead to Alzheimer’s.

What causes Parkinson’s, Alzheimer’s and dementia is the accumulation of certain proteins in the brain, specifically the ‘tau’ protein. When there’s too many of these proteins in the brain, they become toxic and cause neural degeneration. It’s sort of like the plaque which causes tooth decay, which is why scientists refer to this protein build-up as ‘neural plaque’.

“Scientists in the field have been focusing mostly on the final stages of Alzheimer’s disease,” said first author Dr. Cristian Lasagna-Reeves, postdoctoral fellow at the Baylor College of Medicine. “Here we tried to find clues about what is happening at the very early stages of the illness, before clinical irreversible symptoms appear, with the intention of preventing or reducing those early events that lead to devastating changes in the brain decades later.”

Neurons, like any cell, control the amount of protein they make through enzymes. There are, however, literally thousands of enzymes that might be involved with tau accumulation. If you thought what came next was some sly move to help sort through all of these possibilities, I’m sorry to break it to you: there wasn’t. The team went at it the old fashion way, inhibiting enzymes called kinases one by one.

“We inhibited about 600 kinases one by one and found one, called Nuak1, whose inhibition resulted in reduced levels of tau,” said Dr. Huda Zoghbi, professor of molecular and human genetics at Baylor.

Brain section from mouse carrying the dementia-causing P301S mutation in human tau shows accumulation of tau neurofibrillary tangles (in dark brown, left). When Nuak1 levels are decreased by 50% (P301S/Nuak1+/-; right), fewer tau tangles accumulate. Credit: Cell

Brain section from mouse carrying the dementia-causing P301S mutation in human tau shows accumulation of tau neurofibrillary tangles (in dark brown, left). When Nuak1 levels are decreased by 50% (P301S/Nuak1+/-; right), fewer tau tangles accumulate. Credit: Cell

The researchers screened the enzymes by studying them in human cells cultured in a dish, but also in genetically modified fruit flies. Due to their short breeding cycle, the fruit flies proved ideal as it would have otherwise taken countless years to screen as many enzymes in a rodent model, for instance. Human cultured cells, while useful, “cannot model complex nervous system functions,” said Dr. Juan Botas, professor of molecular and human genetics at Baylor.

Next, they put their results to the test by trying to replicate them in a mouse model — and they were successful, as reported in the journal Neuron.

“We found one enzyme, Nuak1, whose inhibition consistently resulted in lower levels of tau in both human cells and fruit flies,” said Zoghbi. “Then we took this result to a mouse model of Alzheimer’s disease and hoped that the results would hold, and they did. Inhibiting Nuak1 improved the behavior of the mice and prevented brain degeneration.”

“Confirming in three independent systems – human cells, the fruit fly and the mouse –   that Nuak1 inhibition results in reduced levels of tau and prevents brain abnormalities induced by tau accumulation, has convinced us that Nuak1 is a reliable potential target for drugs to prevent diseases such as Alzheimer’s,” said Zoghbi. “The next step is to develop drugs that will inhibit Nuak1 in hope that one day would be able to lower tau levels with low toxicity in individuals at risk for dementia due to tau accumulation.”

Armed with this biological mechanism at hand, it’s possible to design drugs that target it and keep dementia at bay. Maybe, not all that different from drugs that lower cholesterol, thus preventing  atherosclerosis and heart disease.

“When people started taking drugs that lower cholesterol, they lived longer and healthier lives rather than dying earlier of heart disease,” said Zoghbi. “Nobody has thought about Alzheimer’s disease in that light. Tau in Alzheimer’s can be compared to cholesterol in heart disease. Tau is a protein that when it accumulates as the person ages, increases the vulnerability of the brain to developing Alzheimer’s. So maybe if we can find drugs that can keep tau at levels that are not toxic for the brain, then we would be able to prevent or delay the development of Alzheimer’s and other diseases caused in part by toxic tau accumulation.”

An antibody that clears Alzheimer’s patients’ brains of plaque could be the treatment we’ve been waiting for

A recent breakthrough has left scientists “trying not to get too excited” as a new antibody cleared all visible signs of Alzheimer’s disease from human subjects’ brains.

Brain scans of Alzheimer’s patients, showing how different doses of the drug reduced the number of amyloid plaques, in red, over a year. Image credits Sevigny et al.

A novel drug based on immune cells harvested from elderly patients aged up to 100 who show no signs of Alzheimer’s could finally allow us to treat the degenerative brain condition. Small-scale human trials led by scientists at pharmaceutical companies Biogen and Neurimmune showed that the drug aducanumab can completely clear the visible signs of Alzheimer’s from the brain.

The team scanned the brains of patients as they were undergoing treatment with the drug. They found that after a year, almost all of the toxic amyloid plaques that build up in their brains were cleared in patients given the highest antibody dose. The scientists also said the patients showed signs that the rate of their cognitive decline had slowed.

Amyloid is a protein found throughout the body but for unknown reasons, in Alzheimer’s patients, it divides imperfectly, creating beta amyloids which are toxic to brain cells and accumulate as plaques on the outside of neurons. The trial’s results suggest that these plaques aren’t a simple byproduct of the condition, but are at least part of what cause it.

The team is understandably very excited about the results.

“Compared to other studies published in the past, the effect size of this drug is unprecedented,” Zurich University Professor and co-author of the paper Roger Nitsch told The Independent.

As part of the trial, different participants received different doses of the drug and a control group which received a placebo treatment.

“One year later, the images of the placebo group are basically unchanged. In the three doses groups, a very clear reduction in amyloid plaques is shown – the higher the dose, the larger the degree of reduction,” Nitsch said.

For the 10mg group, which received the highest dose, the amyloid plaque was almost completely removed.

It’s crucial however that we don’t jump ahead of ourselves here. Aducanumab has been seen to work, but only in a small-scale study. Until the results are reproduced at a larger scale, the drug’s effectiveness is still unproven. If the results are confirmed in larger trials, the drug could become out best tool to cure the condition. Until then, however, as Arizona University Professor Eric Reiman commented in a separate article in Nature:

“Although the authors’ additional cognitive findings are encouraging, they are not definitive. It would be prudent to withhold judgement about aducanumab’s cognitive benefit until results from the larger trials are in.”

However, he shares the enthusiasm of the team for their findings.

“Confirmation that an anti-amyloid plaque treatment slows cognitive decline would be a game-changer for how we understand, treat and prevent Alzheimer’s disease. Now is the time to find out.”

Other experts in the field also have high hopes for the drug but try to keep an objective outlook on the trials. For example, Dr Tara Spires-Jones, interim director of Edinburgh University’s Centre for Cognitive and Neural Systems, said the research showed that the antibody “robustly reduced amyloid pathology in a small group of people in very early stages of the disease”. She said she’s optimistic about the treatment but is trying “not to get too excited” as many drugs that seem promising in small-scale tests fail when scaled up.

Dr James Pickett, head of research at the Alzheimer’s Society, said that the “results are the most detailed and promising that we’ve seen for a drug that aims to modify the underlying causes of Alzheimer’s disease”.

“The study showed that the drug was first able to remove clumps of amyloid – a toxic protein associated with Alzheimer’s – from the brain of mice and also, excitingly, in people. What is most compelling is that more amyloid was cleared when people took higher doses of the drug,” he added.

“No existing treatments for Alzheimer’s directly interfere with the disease process – and so a drug that actually slows the progress of the disease by clearing amyloid would be a significant step.”

He noted that there is evidence of side-effects such as headaches associated with the drug and that the initial trial had not been designed to measure whether the drug slowed the decline in memory and thinking. Pickett too is waiting for the results of larger trials — some already underway in the Uk — to better understand if and how the drug works.

Gordon Wilcock, emeritus professor of geratology at Oxford University, hopes that the trials will bear fruit despite the fact that similar strategies have previously failed to pan out.

“We have already had previous trials of various anti-amyloid strategies, especially the monoclonal antibodies, that have failed to deliver at phase three.

“Nevertheless these trials are justified by the data and I hope they are successful, despite my feelings of déjà vu!”

The full paper, titled “The antibody aducanumab reduces Aβ plaques in Alzheimer’s disease” was published in the journal Nature.

Study finds why men have a better sense of direction

Each sex’s take on navigating through the world around us, and especially the differences between them, is a subject that often surfaces during stand-up acts and day-to-day humour; “Women can’t drive,” or “men never stop to ask for directions” are all things you’ve probably heard before and to an extent, believe. There’s a kernel of truth here; it’s been well established experimentally that men in general handle specific spacial tasks better than the fairer sex.

But what generates these different takes on the same problem? It’s not the brain — we know that for all intents and purposes, brains can’t be distinguished by sex (but they do form connections differently). Cultural conditioning, upbringing and other factors certainly play a part in this, and that can’t be quantified. But Norwegian University of Science and Technology (NTNU) team was interested in the effect of something we can quantify — sexual hormones.

The researchers created two teams of 18 members, divided by sex, and asked them to orient themselves through a very large virtual maze using 3D goggles and a joystick, while the researchers looked at their neural activity.

Study explains why men tend to have a better sense of direction than women.
Image via psypost

Who wants to be a Maze runner?

After familiarizing themselves with the maze for an hour, the subjects were strapped to a fMRI scanner and their brain activity was recorded while the tests progressed. They were given 45 navigational tasks (such as “find the yellow car” from different starting points) and 30 seconds to solve each one of them in.

“Men’s sense of direction was more effective. They quite simply got to their destination faster,” says Carl Pintzka, a medical doctor and PhD candidate at NTNU’s Department of Neuroscience.

The men solved 50 per cent more of the tasks than the women. The recordings show that men took several shortcuts, relied on cardinal directions to a greater degree and, more importantly for Pintzka, used a different part of the brain to orient themselves than the women in the study. And this is the reason why the guys were able to solve more of the tasks; using cardinal directions allows for a much greater flexibility while navigating, and lends itself better to reaching a known point from an unknown position as long as you know where you have to go.

“If they’re going to the Student Society building in Trondheim, for example, men usually go in the general direction where it’s located. Women usually orient themselves along a route to get there, for example, ‘go past the hairdresser and then up the street and turn right after the store’,” he says.

1-0 for the dudes, time for round two

The fMRI scans showed that navigating through space is a complex process — large areas of the brain are involved in orienting ourselves, but there are some key differences. In men, the team saw more activity in the hippocampus, whereas women tended to show more activation in the frontal areas of the brain.

“That’s in sync with the fact that the hippocampus is necessary to make use of cardinal directions,” says Pintzka.

And, from an evolutionary point of view, these results make perfect sense. While our brains are structurally the same, gender roles in those primitive human communities meant that they had to be good at different tasks.

“In ancient times, men were hunters and women were gatherers. Therefore, our brains probably evolved differently. For instance, other researchers have documented that women are better at finding objects locally than men,” Pintzka says.

In simple terms, women are faster at finding things in the house, and men are faster at finding the house.”

A little testosterone under the tongue

The next step was to try and see if the women’s brains could be made to navigate similarly to that of the men.

This time, 42 women were divided into two groups, receiving either a drop of testosterone or placebo under the tongue. To increase accuracy, the team used a double-blinded test so that neither Pintzka nor the subjects knew who got what.

“We hoped that they would be able to solve more tasks, but they didn’t. But they had improved knowledge of the layout of the maze, and they used the hippocampus to a greater extent, which tends to be used more by men for navigating,” says Pintzka.

Pintzka’s research could offer doctors insight into Alzheimer’s disease. As two in three patients are female and loss of direction is one of the first symptoms.

“Almost all brain-related diseases are different in men and women, either in the number of affected individuals or in severity. Therefore, something is likely protecting or harming people of one sex. Since we know that twice as many women as men are diagnosed with Alzheimer’s disease, there might be something related to sex hormones that is harmful,” says Pintzka.

He hopes that by understanding how men and women use different brain areas and strategies to navigate, researchers will be able to enhance the understanding of the disease’s development, and develop coping strategies for those already affected.

The paper can be found online here.

Photo: Janet Stephens

Drug reverses Alzheimer’s effects in rats

There’s no cure for Alzheimer’s – the devastating neurodegenerative disease which causes progressive dementia in 5.3 million Americans – only treatments that help slow down a certain outcome. A milestone research may have finally broken the dry spell in Alzheimer’s research looking for the much sought after cure. While current drugs help mask symptoms, a intravenous drug developed by US researchers actually treats the disease itself with patients showing marked improvements in memory and cognition. At the brain level, new blood vessel formation and an increase in neuronal cell counts was registered. The bad news is that the Alzheimer’s patients are rats and experience has taught us that Alzheimer’s research seldom translates to humans. Seldom, not never though.

Photo: Janet Stephens

Photo: Janet Stephens

Alzheimer’s affects a receptor class called Endothelia B-type in the brain and has been the therapeutic target for a range of research on the disease. Stimulating these receptors showed to offer protection to the nervous system. So, the researchers targeted the receptor with a substance called IRL-1620, which activates the receptor acting as an agonist. An agonist is the opposite of an antagonist, meaning that it binds and activates a receptor – the antagonist blocks it.

After delivering the substance intravenously, the researchers notice a couple of marked improvements only 15 days after the treatment. The rats, which had Alzheimer’s genetically induced, showed improved memory deficit by 50-60% and reduced oxidative stress by 45-50%. Best of all, though, they found new blood vessels and neurons formed in the brain. This shows that Alzheimer’s symptoms have not only been masked, but reversed as reported in the journal Neuroscience.

“We also found that treatment with IRL-1620 enhanced certain recovery processes within the [Alzheimer’s disease]-damaged brain, resulting in more new blood vessels and neuronal cells,” said Seema Briyal, a senior scientist and adjunct assistant professor at Midwestern University in Downers Grove, IL.. “This indicates reparative processes occurring in the damaged brain.”

This is the first research that proves IRL-1620 can reverse Alzheimer’s in an animal model, but from rat to human there’s a long way to go. Besides the inherent differences between, well, rodent and human, these sort of findings are skewed by the fact the diseased rats themselves don’t have a perfectly analogous form of Alzheimer’s. Typically a gene or set of genes are inserted into a rat that causes amyloid beta protein to accumulate in the rats brain which we believe makes up the plaques found in the brains of Alzheimer’s patients. This leads to the formation of a range of clinical and pathological features of Alzheimer’s disease, including cognitive and behaviour deficits, amyloid plaques, neurofibrillary tangles, synapse and neuron loss and neurodegeneration. We currently don’t have a mouse or rat which can develop all the same features of Alzheimer’s disease as humans.

When a trial based on a rodent animal model is assessing whether a treatment works at removing Alzheimer’s disease pathology from the brain, it is unlikely to translate into human studies in the same way. The best models, some scientists believe, are not genetically modified rats, but those elderly rats that develop the disease naturally, just like us humans.

Considering the promising findings, however, we can only hope that this might work on humans, although it’s a cumbersome process. The clinical trials would have to work with a lot of dosages and counting the blood vessels and neurons isn’t that viable. The rats in these studies had to be sacrificed to have their brains dissected. Let’s hope for the best.

http://images.gizmag.com/hero/alzheimers-dementia-cure-yale-amyloid-treatment-9.jpg

Ultrasound treatment restores memory in Alzheimer’s plagued mice

Previously, ultrasounds were used to activate tiny nanobubbles and release drugs past the blood-brain barrier. This is the first time however that ultrasounds alone were demonstrated to improve memory in mice. Professor Jürgen Götz, the director of the Clem Jones Centre for Ageing Dementia Research in Australia and one of the study’s authors, said:

“We’re extremely excited by this innovation of treating Alzheimer’s without using drug therapeutics.

The ultrasound waves oscillate tremendously quickly, activating microglial cells that digest and remove the amyloid plaques that destroy brain synapses.

The word ‘breakthrough’ is often mis-used, but in this case I think this really does fundamentally change our understanding of how to treat this disease, and I foresee a great future for this approach.”

Alzheimer’s is linked to neurotoxic amyloid plaques that cause memory loss and cognitive decline. Plaques consist of largely insoluble deposits of an apparently toxic protein peptide, or fragment, called beta-amyloid. We now know that some people develop some plaques in their brain tissue as they age.

Götz’s team genetically modified mice to produce amyloid plaques, then treated these with focused ultrasound beams which stimulate microglial cells. These are part of the brain’s immune system, and once activated they engulf and absorb the plaques. The ultrasound sessions almost completely cleared the plaques in 75% of the animals, without apparent damage to brain tissue.

We still do not know whether amyloid plaques themselves cause Alzheimer’s or whether they are a by-product of the Alzheimer’s disease process. Even so, the mice who had their plaques cleared showed improved memory comparable to normal mice.

Professor Götz said:

“This treatment restored memory function to the same level of normal healthy mice.

We’re also working on seeing whether this method clears toxic protein aggregates in neurodegenerative diseases other than Alzheimer’s and whether this also restores executive functions, including decision-making and motor control.”

The researchers said a human clinical trial is years away. They envision a mobile device that can be taken home by patients and used several times a year. This could be much more effective than any Alzheimer’s treatment currently used. A lot cheaper too, considering treatments can be as stiff as $25,000.

“With an ageing population placing an increasing burden on the health system, an important factor is cost, and other potential drug treatments using antibodies will be expensive

In contrast, this method uses relatively inexpensive ultrasound and microbubble technology which is non-invasive and appears highly effective,” according to Gotz.

The next trial is slated to test whether the treatment also works on sheep. Findings appeared in the journal Science Translational Medicine.

Studies have shown that anxiety in MCI is associated with abnormal concentrations of plasma amyloid protein levels and T-tau proteins in cerebrospinal fluid, which are biomarkers of Alzheimer’s. Photo: Therapy Ideas

Anxiety can damage the brain and foster Alzheimer’s

Researchers at Baycrest Health Sciences’ Rotman Research Institute have found that patients diagnosed with mild cognitive impairment (MCI) who also show anxiety symptoms are at a much greater risk of developing Alzheimer’s. This was the first study of its kind that isolated anxiety in a longitudinal study covering people diagnosed with MCI, painting a clearer picture of how anxiety interferes with cognitive functions and how it can lead to brain damage.

Why don’t we forget about anxiety?

 Studies have shown that anxiety in MCI is associated with abnormal concentrations of plasma amyloid protein levels and T-tau proteins in cerebrospinal fluid, which are biomarkers of Alzheimer’s. Photo: Therapy Ideas

Studies have shown that anxiety in MCI is associated with abnormal concentrations of plasma amyloid protein levels and T-tau proteins in cerebrospinal fluid, which are biomarkers of Alzheimer’s. Photo: Therapy Ideas

Anxiety is a natural, normal response to potential threats, which puts your body into a heightened state of awareness. There’s a reason we have the ability to feel it, since it evolved as a beneficial sensation. Basically, it’s there to keep you away from harm’s way. If you’re hiking by a steep cliff, you’ll become anxious and thus more careful so you don’t fall off. For an estimated 40 million US adults, however, anxiety may occur even when there’s no real threat, causing unnecessary stress and emotional pain. The National Institute of Mental Health describes anxiety’s relation to the brain as follows:

“Several parts of the brain are key actors in the production of fear and anxiety… scientists have discovered that the amygdala and the hippocampus play significant roles in most anxiety disorders.

The amygdala is an almond-shaped structure deep in the brain that is believed to be a communications hub between the parts of the brain that process incoming sensory signals and the parts that interpret these signals. It can alert the rest of the brain that a threat is present and trigger a fear or anxiety response.

The emotional memories stored in the central part of the amygdala may play a role in anxiety disorders involving very distinct fears, such as fears of dogs, spiders, or flying. The hippocampus is the part of the brain that encodes threatening events into memories.”

Literature identifies late-life depression as a significant risk marker for Alzheimer’s. Anxiety differs from the general symptoms of depression, yet traditionally anxiety has been subsumed under depression. As such, while depression is routinely screened, anxiety is not, and as we’ll see from the study’s findings this might need to change.

In contrast to Alzheimer’s disease (AD) where other cognitive skills are affected, mild cognitive impairment (MCI) is defined by deficits in memory that do not significantly impact daily functioning. Memory problems may be minimal to mild and hardly noticeable to the individual. For most people, memory deficits from MCI stabilize in a couple of years, while in others memory ability can be recovered. However, MCI has been proven to be a significant risk marker for developing Alzheimer’s.

Anxiety, stress and lost car keys

Alzheimer’s disease is progressive in nature, meaning that it is not reversible, and it eventually leads to death.  Every case of AD is different but the ultimate path of the disease is somewhat predictable and occurs slowly over the course of 2-20 years.  It generally starts with deterioration in the Hippocampus, an inner structure of the brain associated with memory and learning.  The disease then tends to spread from front to back of the cerebral cortex, until reaching the brain stem, where involuntary functions such as breathing, heart rate and blood pressure are regulated. Image: Wikimedia Commons

Alzheimer’s disease is progressive in nature, meaning that it is not reversible, and it eventually leads to death. Every case of AD is different but the ultimate path of the disease is somewhat predictable and occurs slowly over the course of 2-20 years. It generally starts with deterioration in the Hippocampus, an inner structure of the brain associated with memory and learning. The disease then tends to spread from front to back of the cerebral cortex, until reaching the brain stem, where involuntary functions such as breathing, heart rate and blood pressure are regulated. Image: Wikimedia Commons

Linda Mah, clinician-scientist with Baycrest’s Rotman Research Institute, and assistant professor in the Department of Psychiatry at the University of Toronto, led a team that analyzed data from the large population-based Alzheimer’s Disease Neuroimaging Initiative to analyze anxiety, depression, cognitive and brain structural changes in 376 adults, aged 55 – 91, over a three-year period. The patients were surveyed with follow-up assessments every six months. All of the adults had a clinical diagnosis of amnestic MCI and a low score on the depression rating scale, indicating that anxiety symptoms were not part of clinical depression.

[ALSO SEE] Magic Mushrooms can treat depression, anxiety and addiction, study shows

The MCI patients who were also diagnosed with anxiety had a much greater chance of experiencing a sharp decline in cognitive functions. For MCI patients with mild, moderate or severe anxiety, Alzheimer’s risk increased by 33 percent, 78 percent and 135 percent respectively.

“Our findings suggest that clinicians should routinely screen for anxiety in people who have memory problems because anxiety signals that these people are at greater risk for developing Alzheimer’s,” said Mah.

The study shows that anxiety can be a predictive factor in MCI patients of whether or not these will convert to Alzheimer’s. As such, clinicians should take special notice and screen MCI patients for anxiety as well. No treatment is currently available for MCI, but there are many solutions to address anxiety, from therapy, to diet, to exercising.

“While there is no published evidence to demonstrate whether drug treatments used in psychiatry for treating anxiety would be helpful in managing anxiety symptoms in people with mild cognitive impairment or in reducing their risk of conversion to Alzheimer’s, we think that at the very least behavioural stress management programs could be recommended. In particular, there has been research on the use of mindfulness-based stress reduction in treating anxiety and other psychiatric symptoms in Alzheimer’s and this is showing promise,” said Mah.

The findings were reported by The American Journal of Geriatric Psychiatry, ahead of print publication, scheduled for May 2015.

Light/Moderate Alcohol Consumption associated with better Memory in Later Life

Alcohol is generally regarded as unhealthy, with a myriad of long-term negative effects and even short term negative effects. But there are still many things we don’t understand about how alcohol interacts with out bodies. For example, a 2011 Texas research found that alcohol consumption helps some areas of our brain remember better, while a 2005 study showed that moderate alcohol consumption lowers the risk of type 2 diabetes. Now, a new study suggests that low or moderate alcohol consumption is correlated with higher episodic memory and larger hippocampal brain volume.

A glass of wine may do wonders for your health – but more will certainly harm it. Image via The Telegraph.

“The findings from this study provide new evidence that hippocampal volume may contribute to the observed differences in episodic memory among older adults and late life alcohol consumption status”, authors write in the study.

Now, let’s just settle one thing right off the bat – correlation does not imply causation. The fact that alcohol consumption is correlated with better episodic memory doesn’t mean that the alcohol is the cause here. This being said, previous studies conducted on animals have also suggested that moderate alcohol consumption could promote generation of new nerve cells in the hippocampus. The hippocampus one of the crucial parts of the brain, responsible for storing memory and navigating through space. While it’s pretty clear that the hippocampus is involved in many other things, it’s still not clear what those things are. What is clear is that during Alzheimer’s disease, this is the area which suffers the most damage.

Now, this study has found not only that light consumption of alcohol is not detrimental, but that it can in fact help your brain.

“There were no significant differences in cognitive functioning and regional brain volumes during late life according to reported midlife alcohol consumption status,” said lead author Brian Downer. “This may be due to the fact that adults who are able to continue consuming alcohol into old age are healthier, and therefore have higher cognition and larger regional brain volumes, than people who had to decrease their alcohol consumption due to unfavourable health outcomes.”

What is important to keep in mind here is that while low alcohol consumption may have some benefits, extended periods of abusing alcohol is well known to cause damage to the brain. So, to sum it up, no one is saying “Don’t drink alcohol at all” – it’s just that if you want to drink, one or two glasses is more than enough.

Journal Reference: Downer B, Jiang Y, Zanjani F, Fardo D. Effects of Alcohol Consumption on Cognition and Regional Brain Volumes Among Older Adults. Am J Alzheimers Dis Other Demen. 2014 Sep 7.

Effects of Alzheimer's. Image: healthbenefitstimes.com

Chemical switch found in Alzheimer’s and stroke victims’ brains kills neurons

Effects of Alzheimer's. Image: healthbenefitstimes.com

Effects of Alzheimer’s. Image: healthbenefitstimes.com

Researchers at the Sanford-Burnham Medical Research Institute (Sanford-Burnham) have found a chemical switch that both regulates the generation of new neurons from neural stem cells and the survival of existing nerve cells in the brain. Postmortem examination of the brains of Alzheimer’s patients and stroke victims found the switch that shuts off the signals was in abundance. With this in mind, it’s possible that a drug that targets the switch, called MEF2, might prevent neuronal loss in a variety of neurodegenerative diseases, such as Alzheimer’s, Parkinson’s and autism.

“We have shown that when nitric oxide (NO)—a highly reactive free radical—reacts with MEF2, MEF2 can no longer bind to and activate the genes that drive neurogenesis and neuronal survival,” said Stuart Lipton, M.D., Ph.D., director and professor in the Neuroscience and Aging Research Center at Sanford-Burnham, and a practicing clinical neurologist. “What’s unique here is that a single alteration to MEF2 controls two distinct events—the generation of new neurons and the survival of existing neurons,” added Lipton, who is senior author of the study.

Switching new neurons on and off

Transcription factors are proteins that control which genes are turned on or off in the genome. They do so by binding to DNA and other proteins. Once bound to DNA, these proteins can promote or block the enzyme that controls the reading, or “transcription,” of genes, making genes more or less active. In the brain, the transcription factors are paramount to linking external stimuli to protein production, enabling neurons to adapt to changing environments. Previous research showed that the MEF2 family of transcription factors plays an important part in the neurogenesis and neuronal survival, as well as in the processes of learning and memory. On the opposite side, MEF2 mutations have been linked with neurodegenerative disorders, including Alzheimer’s and autism.

The NO-protein modification process mentioned by Lipton earlier was first described him and his collaborators some 20 years ago (S-nitrosylation). S-nitrosylation involves the covalent incorporation of a nitric oxide moiety into thiol groups, to form S-nitrosothiol (SNO). S-nitrosylation of MEF2 controlls neuronal survival in Parkinson’s disease and has important regulatory functions under normal physiological conditions throughout the body.

“Now we have shown that this same reaction is more ubiquitous, occurring in other neurological conditions such as stroke and Alzheimer’s disease. While the major gene targets of MEF2 may be different in various diseases and brain areas, the remarkable new finding here is that we may be able to treat each of these neurological disorders by preventing a common S-nitrosylation modification to MEF2.”

“The findings suggest that the development of a small therapeutic molecule—one that can cross the blood-brain barrier and block S-nitrosylation of MEF2 or in some other way increase MEF2 transcriptional activity—could promote new brain cell growth and protect existing cells in several neurodegenerative disorders,” added Lipton.

“We have already found several such molecules in our high-throughput screening and drug discovery efforts, so the potential for developing new drugs to attack this pathway is very exciting,” said Lipton.

The study was published in Cell Reports.

alzheimers

Genetic variant explains why women are more prone to Alzheimer’s

Alzheimer's

Photo: e-manonline.com

Like a sticking nail, Alzheimer’s has been irritating neuroscientists for decades. After so many years and billions worth of research, the underlying causes and mechanics that cause the gruesome neurodegenerative disease have yet to be identified, though hints suggest genetics have a major role to play – never mind a cure! Clearly, Alzhaimer’s is formidable and while we’ve yet to fully understand it, scientists are doing their best and every year there seems to be a new piece added that might one day fit the whole puzzle.

For instance, a team of researchers at Stanford confirmed earlier findings that suggests a genetic variant makes women more prone to the disease than men. This is evidence that the disease affects genders unequally and suggests that future treatment should be prescribed gender specific.

It’s those genes

In 1993, researchers found that elders who inherit a gene variant called apolipoprotein E4 (APOE4) are more prone to the common form of Alzheimer’s that strikes in late life. Other variants have also been identified as being linked with Alzheimer’s: APOE3, the risk neutral variant, and the much rarer variant APOE2, which actually decreases a person’s risk of developing Alzheimer’s. A bit later, in 1997, researchers combed through more than 40 studies and analyzed data pertaining to  5930 Alzheimer’s patients and 8607 dementia-free elderly and found females with the APOE4variant were four times more likely to have Alzheimer’s compared with people with the more common, neutral form of the gene.

alzheimers

Photo: triumf.ca

That’s a really big difference, but for some reason the findings didn’t become that widely known. Michael Greicius, a neurologist at Stanford University Medical Center in California re-discovered the findings in 2008 and decided it was worth making a new investigation. He and his team first performed some neuroimaging on patients and found from the brain scans that  women with the APOE4 variant had poor connectivity in brain networks typically afflicted by Alzheimer’s, even though there weren’t any symptoms for Alzheimer’s present in the first place. This was fishy.

A more comprehensive view

Greicius and colleagues settled they would have to perform a longitudinal study on this to see the full extent of this genetic variance, so they pulled data from 2588 people with mild cognitive impairment and 5496 healthy elderly who visited national Alzheimer’s centers between 2005 and 2013. Every participant was logged according to genotype (did he have the APOE4 or APOE2?) and gender. Most importantly, each participant was surveyed in follow-up studies to see if the mild impairments had grown into full-blown Alzheimer’s.

Confirmed that the APOE4 is a risk gene, males and females participants with mild cognitive disabilities who were identified carrying the gene  variant equally progressed to Alzheimer’s disease more readily than those without  the gene.  However, among healthy seniors, women who inherited the APOE4 variant were twice as likely as noncarriers to develop mild cognitive impairment or Alzheimer’s disease, whereas APOE4 males fared only slightly worse than those without the gene variant. This is a full step ahead of the previous 1997 study because it tell us more about how the gene variant potentially leads to Alzheimer’s, especially in women.

The findings will most likely have significant implications in how Alzheimer’s is treated. Interestingly enough, some previous studies, according to the researchers, have shown that there are some side effects when treating patients that carry the APOE4 variant, but these studies were not subdivided according to gender.  Moreover, it’s possible that some treatments are more effective to treating symptoms for men more than women, and this is something definitely worth taking into account.

 

For the first time, scientists show coffee works against Alzheimer’s disease

As part of a German-French research project, a team led by  Dr. Christa E. Müller from the University of Bonn and Dr. David Blum from the University of Lille was able to demonstrate that coffee consumption works against Alzheimer’s disease.

With coffee, it’s a “one step further two steps back” dance. Its benefits, when consumed occasionally include a huge amount of antioxidants, burning fats, stimulating the brain, a lower chance of diabetes, etc. The problem is that very few people drink coffee occasionally. Most coffee drinkers drink it every single day, and by now, it’s safe to say that it’s a form of addiction; and when you consume it in large quantities, the downsides clearly start to outweigh the benefits. Many cardiovascular problems, increased risk of osteoporosis and diabetes, stomach problems, stained teeth, grumpiness, lack of energy, the list could go on and on.

Furthermore, it has to be said that most of the studies proclaiming the benefits of coffee are actually funded by coffee companies… which puts a big dent in their credibility (not saying that a study is wrong just because it is funded by a biased company, but you have to take it with an extra grain of salt). This study however was funded by non-profit Alzheimer Forschung Initiative e.V. and French Partner organization LECMA – also an Alzheimer related organization.

What they showed was that coffee has a positive effect against tau deposits, the characteristic features of Alzheimer’s disease. Tau deposits are a type of protein which disrupts the communication of the nerve cells in the brain and contribute to their degeneration; it is not clear however that fighting tau deposits would counter all the effects of Alzheimer’s, but it’s a really good start. However, despite intensive research there is no drug available to date  which can prevent this detrimental process. Based on this study, a new caffeine drug might be developed with success.

They conducted their study on lab mice genetically altered to develop Alzheimer’s, which were split up in two groups – one which didn’t receive any treatment, and the other which received a caffeine-based treatment. The second group performed much better when it came to memory-related tasks, an amelioration of the pathogenic processes was demonstrated in the hippocampus, which is the site of memory in rodents – tau deposits were much less developed after the treatment was applied.

“We have taken a good step forward,” says Prof. Müller. “The results of the study are truly promising, since we were able to show for the first time that A2A adenosine receptor antagonists actually have very positive effects in an animal model simulating hallmark characteristics and progression of  the disease. And the adverse effects are minor.”

Science Reference.

 

Brain tissue from a mouse shows star-shaped astrocytes (green). Cells (blue) containing mutant protein (white) display lower levels of a potassium-regulating protein (red). Photo: UCLA

Tweaking potassium in brain cells helps fight Huntington’s disease

Brain tissue from a mouse shows star-shaped astrocytes (green). Cells (blue) containing mutant protein (white) display lower levels of a potassium-regulating protein (red). Photo: UCLA

Brain tissue from a mouse shows star-shaped astrocytes (green). Cells (blue) containing mutant protein (white) display lower levels of a potassium-regulating protein (red). Photo: UCLA

Approximately one in 20,000 Americans suffer from Huntington’s disease, a devastating neurodegenerative affliction that  gradually deprives patients of their ability to walk, speak, swallow, breathe and think clearly. Like other similar diseases, like Alzheimer’s, there isn’t any cure, but scientists at University of California, Los Angeles (UCLA) may have discovered a way to tackle it by looking elsewhere than other researchers. Namely, by boosting the potassium intake ability of a specific cell in the brain, the UCLA researchers improved walking and prolonged survival in a mouse model of Huntington’s disease.

Huntington’s disease is passed from parent to child through a mutation in the huntingtin gene, namely a genetic defect on chromosome 4. The defect causes a part of DNA, called a CAG repeat, to occur many more times than it is supposed to. Normally, this section of DNA is repeated 10 to 28 times. But in persons with Huntington’s disease, it is repeated 36 to 120 times.  As the gene is passed down through families, the number of repeats tend to get larger. The larger the number of repeats, the greater your chance of developing symptoms at an earlier age. Therefore, as the disease is passed along in families, symptoms develop at younger and younger ages.

After onset, the disease gradually kills neurons causing the dreaded symptoms, while patients with aggressive cases can die in as little as 10 years. Most research has concentrated on neurons and their mechanics, looking on how these interact and how these genetic malfunctions cause Huntington’s. The UCLA researchers, however, took an alternate route and looked at what role astrocytes — large, star-shaped cells found in the brain and spinal cord — play in Huntington’s.

The stellar nebula in the brain

Artist impression of astrocytes. Photo: UCLA

Artist impression of astrocytes. Photo: UCLA

Astrocytes appear in almost equal number as neurons and enable the latter  to signal each other by maintaining an optimal chemical environment outside the cells. The scientists used two mouse models to explore whether astrocytes behave differently during Huntington’s disease: the first model studied an aggressive and early-onset type of Huntington’s; the second a slow-developing version.

In both models, astrocytes with the mutant gene showed a measurable drop in Kir4.1, a protein that allows the astrocyte to take in potassium through the cell membrane. This caused too much potassium to accumulate around the cell, disrupting the delicate chemical balance and causing neurons to grow oversensitive and fire too easily, disrupting nerve-cell function and ultimately the body’s ability to move properly. Ultimately this may be what causes the jerky motions common to Huntington’s disease.

To test if this hypothesis is correct, the researchers sought to find what would happen if they artificially increased Kir4.1 levels inside the astrocytes.  The results speak for themselves.

“Boosting Kir4.1 in the astrocytes improved the mice’s ability to walk properly,” said  Baljit Khakh, a UCLA professor of physiology and neurobiology. “We were surprised to see the length and width of the mouse’s stride return to more normal levels. This was an unexpected discovery.”
“Our work breaks new ground by showing that disrupting astrocyte function leads to the disruption of neuron function in a mouse model of Huntington’s disease,” said Michael Sofroniew, a UCLA professor of neurobiology. “Our findings suggest that therapeutic targets exist for the disorder beyond neurons.”
“We’re really excited that astrocytes can potentially be exploited for new drug treatments,” said Khakh. “Astrocyte dysfunction also may be involved in other neurological diseases beyond Huntington’s.”
Next, the researchers plan on exploring more of the astrocyte-neuron mechanisms in order to find out more how tweaking Kir4.1 levels alters neural networks. Findings appeared in Nature Neuroscience.
dementia prevention

Improving the Quality of Life for People with Dementia

dementia prevention

Photo: guardianlv.com

Caring for a loved one who suffers from dementia is demanding. It often seems like a losing battle too. One thing that caregivers often fail to do is to consider things from the dementia sufferer’s perspective. That’s not to say that it’s easy. Erratic behaviour, miscommunication and other everyday occurrences can quickly erode the patience of just about anyone. Instead of responding to these and other challenges based solely on outward signs, you should make a conscious effort to put yourself in the shoes of the person who is suffering from dementia. This simple switch in perspective can dramatically improve your loved one’s quality of life and make your job much easier too.

Remember that Dementia shouldn’t Define a Person

It’s easy to start defining a loved one based on his or her dementia. That’s particularly true in cases of advanced dementia, when it feels like nearly every interaction is coloured by the person’s illness. However, it’s crucial to remember that dementia is just one aspect of your loved one’s personality. The same personality traits that were always present are generally still there. By pushing past the dementia and focusing on the person below, you will have an easier time seeing life from your loved one’s perspective.

Focus on Your Loved One’s Strengths

Like many caregivers, you may find yourself dwelling on the capabilities and abilities that have diminished since your loved one developed dementia. There is no benefit in doing this, and you should try to switch your way of thinking. Regardless of the severity of your loved one’s illness, he or she still has strengths. There are still positive things on which you can focus, and that is what you should try to do. This is as much for your loved one’s benefit as your own. Instead of thinking, “He used to know how to tie his shoes,” try thinking, “He is still great at drawing!” When you make this switch in thinking, you’re better able to enter your loved one’s world.

Involve Your Loved One in Decisions

It’s often tempting to take the reins whenever a decision needs to be made regarding your loved one. Whether a decision is major or minor, make a point of including him or her in the process. Think of it this way: How would you like it if people made important decisions for you without your input? Remember that your loved one must still care about what happens in his or her life. Although involving your loved one in the decision making process may make it more stressful, it’s the right thing to do.

Learn to Read Behavioural Cues

Although dementia has surely had an effect on how your loved one behaves, it likely hasn’t completely transformed his or her personality. Many times, caregivers view their loved ones as completely different people. This makes it more difficult to read subtle behavioural cues. It’s another example of why you shouldn’t let dementia define your loved one. There is now a “new normal” when it comes to your loved one’s personality, but he or she will still feel and experience the full range of emotions. Learn to spot different emotions in order to respond appropriately.

Safety isn’t All that Matters

Many times, it feels like as long as a dementia sufferer is safe, everything is as good as it can be. When you step inside the mind of a dementia sufferer, however, you’ll quickly see that things like contentment and happiness are equally crucial. From time to time, consider the current circumstances and image being the person with dementia. Would you be happy? What changes could be made to make you happier? Don’t assume that your loved one is content just because he or she isn’t expressing dissatisfaction.

Your Behaviour Affects Your Loved One’s Behaviour

Think about how you feel when you’re around someone who is clearly upset or very anxious. To some degree, you’re apt to start feeling the same way. The behaviour of others affects healthy people’s moods, and it affects dementia sufferers’ moods as well. If you were suffering from dementia, how would you want those around you to behave? As stressful as it can be to be a caregiver, try to remember that your overall mood often has a profound impact on your loved one.

Use Past Experiences to Empathise with Your Loved One

Because you don’t also suffer from dementia, you may feel like there’s no way to understand how your loved one feels. That’s not strictly true, however. All of us have moments or periods of time where we’ve felt lost, confused and anxious. Such emotions and feelings are quite common for dementia sufferers, so a great way to view life from your loved one’s perspective is by recalling such instances in your own life.

After remembering a moment or period of time where you felt lost and confused, consider what could have made you feel better. Sure, a concrete solution might have worked, but perhaps it just wasn’t possible. What could another person have said or done to help? By performing this exercise, you will be able to develop more empathy for your loved one. In turn, you’ll probably have a lot more patience. This will benefit your loved one in many ways. You might even consider talking about your experience with your loved one to demonstrate that he or she is not alone.

Conclusion

As with caring for someone with any kind of illness, there will always be ups and downs when providing care for a person who suffers from dementia. It’s easy to become overwhelmed and to forget that the dementia sufferer is still a multifaceted person who isn’t completely defined by his or her illness. Considering your loved one’s point of view is an excellent way to ensure that you are providing the best care possible. In addition to producing many benefits for your loved one, this way of thinking can make your role as caregiver easier to handle. In the end, your loved one’s quality of life will improve, and you will both be much happier.

alzheimer brain scan

Blood test for Alzheimer’s detects the disease with 90% accuracy

Considering population growth and increased life expectancy, experts estimate that by  2050 some 115 million people will be afflicted by Alzheimer’s disease – a prevailing neurodegenerative disease that needs no introduction. There’s no cure to Alzheimer’s, but there are treatments that help mild symptoms or prolong sanity before the point of no return is reached. All of these treatments, however, require diagnosing the disease early on for them to have any lasting effect. Current methods are difficult, expensive and not that reliable.

Neuroscientists at  University of California (UC) claim it may be possible to predict with 90% accuracy whether older people will develop the disease over the course of 2 to 3 years simply by looking at a blood sample. If these results can be replicated and the method is found reliable, it could potentially revolutionize the way Alzheimer is being treated today, especially considering there are many voices in the medical field today that call for more drug testing in the disease’s early stage in hope that a cure may actually be found.

A blood test for Alzheimer’s?

The most reliable diagnosis tool for Alzheimer’s involves a brain autopsy. Obviously, it’s as useful as a horse with no legs. Next in the line is extracting fluid from the spinal cord and measuring hallmark protein levels, which is damn painful. Less invasive is running brain scan images in search for the same  protein plaques and tangles in brain tissue which mark the disorder. Neither method, except the autopsy, is that reliable though.

In contrast, if found indeed accurate, the sort of blood test the UC researchers perform is extremely simple to do, doesn’t involve any pain or brain slashing, and may prove to be reliable.

alzheimer brain scan

Image shows two brain scans: top healthy brain; bottom alzheimer’s diseased brain. photo: oenolog.ro

The researchers first recruited a couple hundred senior volunteer and collected blood samples, which they then froze and had them shipped to a lab where a mass spectrometer analyzed the blood’s chemical markup to the last molecule. For three years, the progress of the volunteers was followed and   53 people were identified with mild cognitive impairment or Alzheimer’s disease,  18 of whom had not displayed any symptoms at the beginning of the study. Scientists made a comparative analysis of the 53 seniors with Alzheimer’s against 53 other from the same group, chosen at random that were not diagnosed with Alzheimer’s or exhibited any symptoms.

Those who showed mental decline exhibited significant alterations in the blood levels of 10 different chemicals,  including fatty molecules called phospholipids, which help keep cell membranes in the brain and body intact. To see how accurate to truth their correlation was, the researchers then chose 41 volunteers at random to see if they could predict if any of them would get Alzheimer’s. Their analysis proved to be 90% accurate of the time.

This sounds like a huge big deal; and frankly, I think it is. Before these results are replicated with larger groups and by other independent research groups, some scientists advise, it’s best not to get our hopes up just yet. Anyone can get Alzheimer’s, really, a fact reflect by the extremely diverse population of patients. It’s possible that the blood tests performed in the present study only catered to a couple of similarities, but on real tests with millions of patients, it’s possible the blood test might become overwhelmed by too many conditions and fail as a reliable diagnosis tool.

Still, the implications of such a simple tool would be immense and could help millions of people ‘waiting’ to be gripped by dementia prolong their sanity and maybe even aid in developing the next line of treatments that might ultimately lead to a cure. Many such studies “have turned out to be a flash in the pan,” says Robert Green, a medical geneticist at Harvard University, but the new study “is more sophisticated than most.”

Findings were published in Nature Medicine.