Two new studies presented recently at the Alzheimer's Association International Conference in Los Angeles are shedding light on the longstanding mystery of why women suffer from Alzheimer's and dementia at higher rates than men. As well as discovering sex-specific genes associated with Alzheimer's risk, the researchers describe how toxic dementia-causing proteins spread differently through female brains.

Nearly two-thirds of those in America currently living with Alzheimer's disease are women but it is unclear exactly why this is the case. The traditional hypothesis has been that women live longer than men, so of course they would ultimately register higher rates of Alzheimer's. However, age isn't enough to explain this sex-specific difference.

One of the toxic proteins known to accumulate in the brains of those suffering from Alzheimer's is tau. Clumping into what are called neurofibrillary tangles, these abnormal accumulations are one of the causes of neuron death leading to cognitive impairment. A new study from researchers at Vanderbilt University Medical Center used positron emission tomography (PET) brain scans to see if there are differences in the way tau spreads through male and female brains.

The study revealed women suffering from mild cognitive impairment (MCI) displayed very different brain networks of tau tangles than men with the same level of MCI. The speculation from the researchers is that certain sex-specific differences in how brain regions are connected could be accelerating the spread of toxic tau tangles across female brains.

"The differences that we observed indicate the strong possibility that there are sex differences in the structural and functional connections in the brain, which may contribute to women's increased risk for Alzheimer's," says Sepideh Shokouhi, one of the Vanderbilt researchers working on the project.

The other new study presented at the conference revealed 11 different genes with sex-specific Alzheimer's associations. A couple of genes in particular stood out to the researchers as quite relevant. CD1E and PTPRC, both genes which play a role in immune response, were related to heightened Alzheimer's risk in women.

"This research demonstrates that genetics may contribute to differences in risk and progression of Alzheimer's disease between men and women," says Brain Kunkle, a genetic epidemiologist from the University of Miami working on the study. "More research is needed to understand how much these genes contribute to Alzheimer's risk, and whether they can be used to specifically identify men and women at risk for this disease."

Both studies are still yet to be peer-reviewed and published, but they certainly offer intriguing insights into potential biological differences between the sexes that could help us understand why Alzheimer's seems to appear more frequently in women than men. Maria Carrillo, chief science officer from the Alzheimer's Association, points out it's important to understand these sex-specific differences so future treatments can be better administered.

"Understanding these sex-specific differences may help us identify and apply customized prevention strategies for different populations against cognitive decline, Alzheimer's disease and other dementias," says Carrillo.

The new research was presented at the 2019 Alzheimer's Association International Conference in Los Angeles.

Source: AAIC