Research has established that women are twice as likely to develop Alzheimer’s, but despite study after study into this sex-based disparity in Alzheimer’s risk, scientists are still working to understand why. So far, scientists have learned that women have a few risk factors and warning signs that differ from men. Could these risk factors — like genes on the X chromosome and menopause — lead to a better understanding of not only this disparity, but of Alzheimer’s disease and its root cause?
Sex differences haven’t always been front and center in medical research. Until 1993, there was no law in place ensuring that women be included in clinical trials. Even now, two out of three animal-based Alzheimer’s and dementia studies do not take sex into account. Studying these important differences and getting to the bottom of what makes women more vulnerable to Alzheimer’s can help scientists develop better treatments for both women and men.
Sex differences in risk factors for Alzheimer’s
Pregnancy could provide someone with a glimpse into future risk of disease.
High blood pressure during pregnancy — a common condition which will affect one in seven people — is linked to more cognitive decline and brain shrinkage later in life. The high blood pressure may damage blood vessels near the brain, which tripling the risk of developing Alzheimer’s or vascular dementia later in life.
Clues hidden in the X chromosome
Most women carry two copies of the X chromosome while most men only have one copy. This extra copy is normally “shut down” and serves as backup in case something goes wrong. However in some cases, genes from both copies of the X chromosome are produced. A few of these genes are even linked to cognitive aging and protein plaques and tangles in women, but not in men.
Scientists recently linked the production of USP11 — one such X-linked gene — to increased levels of tau accumulation in women. Producing a lot of USP11 means that tau proteins are not destroyed or recycled by cells, instead they start accumulating causing cell death.
Estrogen and menopause: Another piece of the puzzle
While estrogen is commonly known as a sex hormone, it also plays a role in brain signaling. In both men and women, estrogen has neuroprotective properties that may help the brain stay healthy longer. However, during menopause the levels of estrogen sharply decline leading to brain fog. The decline in estrogen may also increase vulnerability to Alzheimer’s and other dementias.
Would increasing estrogen levels through hormone replacement therapy help? So far the research isn’t conclusive but with more scientists on the case, we may know for sure in the coming years.
The bottom line
Women are twice as likely as men to develop Alzheimer’s. Pregnancy provides an early clue about risk — high blood pressure or gestational diabetes suggests that a person’s risk is higher. Fortunately, research into X-linked genes and estrogen might help scientists develop new treatments in the future.
To learn about clinical trials of new medications that aim to modify the pathology of Alzheimer's disease, call Charter Research at 407-337-1000 (Orlando) or 352-775-1000 (The Villages).