The most reliable indicator of Alzheimer's risk is the presence of the APOE gene. However new research shows that it could play a different role in female patients than in males. Scientists at the Vanderbilt Memory and Alzheimer's Center have published research that shows definite gender differences between men and women regarding the influence of the APOE gene as well as differences in the association of the gene and levels of beta-amyloid and tau proteins in the brain.
While women live longer than men, in general, the study, which was published in the journal JAMA Neurology, suggests that the higher rate of Alzheimer's in women isn't merely because they live longer, but instead is explicitly connected to the APOE gene and how it impacts the development of Alzheimer's
In the United States, slightly less than 2/3 of patients diagnosed with Alzheimer's are women. The study conducted by researchers at Vanderbilt looked at a meta-analysis of cerebral spinal fluid (CSF) taken from four different groups of study volunteers. Also included were autopsy findings on the brains of patients who had an Alzheimer's diagnosis show that while the APOE gene is a significant factor in determining risk for developing Alzheimer's, in women it might be a more substantial piece of information than it is in men.
Timothy Hohman, Ph.D., is an assistant professor of Neurology at Vanderbilt and led the research. He explained, "In Alzheimer's disease, we have not done enough to evaluate whether or not sex is a contributing factor to the neuropathology. We haven't fully evaluated sex as a biological variable. But there is good reason to expect in older adulthood that there would be hormonal differences between the sexes that could impact disease."
The study looked at pathways, that is, the mechanism by which APOE is a factor in developing Alzheimer's. There is the amyloid pathway which is where proteins form plaques in the brain or the tau pathway, which are the tangles of protein. Both of these play a role in developing the disease, but there were distinct differences between men and women in the tau pathway. It was a surprise finding for the researchers because the APOE gene already has a well-established role in amyloid processing, but the amyloid pathway was mostly the same in both men and women.
The current hypothesis regarding amyloid and tau is that amyloid comes along first and later on tau changes in the brain are what cause the changes in cognition, memory and other mental function. The research at Vanderbilt indicates that APOE might impact risk along gender lines. While there was a more significant association between tau and gender, the same association was not seen in the autopsy results and datasets. This could be due to Braak staging, which looks at location, rather than tau amounts. It's also possible that tau amounts in CSF indicate a general neurodegenerative decline, that isn't about the tangles of tau that cause Alzheimer's.
The study was beneficial because it suggests that gender should be a variable that is investigated in the biological underpinnings of Alzheimer's, which hasn't been a consideration up until now. Take a look at the video below from the team at Vanderbilt, to learn more about this research.