2022 Spring GAPNA Newsletter Volume 41 Number 1

Sex-Specific Differences in Aging and Alzheimer’s Disease May Be Tied to Genetics

When it comes to cognitive aging and Alzheimer’s disease, the differences between men and women may be related to genetics. According to new research, genes contained in the X chromosome may hold the key to differences between men and women in aging and Alzheimer’s-related cognitive decline.

In a recent study, scientists analyzed genetic and clinical data from a joint cohort consisting of two long-term studies: the Religious Orders Study and the Rush Memory and Aging Project.

Genetic data were gathered from the brain tissue of 508 autopsied individuals via RNA sequencing. Data were also gathered about participants’ cognitive function over several years to assess changes in cognition, including memory and attention. Participants did not have dementia at the time of their enrollment in the studies and were monitored periodically until their death.

Using genetic and clinical data, the scientists examined associations of cognitive changes and levels of neurofibrillary tangles with genes on the X chromosome.

Results showed the expression levels of 19 genes on the X chromosome were linked to changes in cognition and quantity of neurofibrillary tangles. In women, this increased expression was associated with slower cognitive decline.

The expression of these genes was not increased in men. This may suggest specific genes on the X chromosome help protect women from cognitive decline in aging and Alzheimer’s.

In contrast, the expression of three X chromosome genes associated with neurofibrillary tangles was increased in men. This may suggest men could be more at risk of developing Alzheimer’s-related pathological changes than women.

For more info, see Davis, E.J., et al. (2021). Sex-specific association of the X chromosome with cognitive change and tau pathology in aging and Alzheimer disease. JAMA Neurology, 78(10), 1249. https://doi.org10.1001/jamaneurol.2021.2806