Study provides robust evidence of sex differences with Alzheimer’s gene

From the Summer 2018 edition of Vanderbilt Medicine Magazine

 

Illustration by Iker Ayestaran.

The APOE gene, the strongest genetic risk factor for Alzheimer’s disease, may play a more prominent role in disease development among women than men, according to new research from the Vanderbilt Memory and Alzheimer’s Center.

The research confirmed recent studies that carrying the APOE ε4 allele has a greater association with Alzheimer’s disease among women compared to men, and went one step further by evaluating its association with amyloid and tau levels.

The study published May 7 in JAMA Neurology adds to mounting evidence that the higher prevalence of Alzheimer’s disease among women may not simply be a consequence of living longer.

Almost two-thirds of Americans with Alzheimer’s are women. The research, based on a meta-analysis of both cerebral spinal fluid (CSF) samples from study volunteers from four datasets and autopsy findings from six datasets of Alzheimer-diseased brains, is the most robust evidence to date that the APOE gene may play a greater role in women than men in developing Alzheimer’s pathology, said Timothy Hohman, PhD, the study’s lead author.

“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,” he said.

The study looked at whether APOE in men and women was primarily associated with the amyloid pathway — the proteins that form plaques in the brain — or with the tau pathway — the proteins that form tangles in the brain.

The association with the amyloid pathway was the same in men and women. However, the APOE association was much greater for women with the tau pathway. This is opposite of what researchers expected because of APOE’s established role in amyloid processing.