Tag Archives: cognitive disability


Genetic variant explains why women are more prone to 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.


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.