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2022 AD Strategic Fund: APOE Biology in Alzheimer's (ABA) (ABA)

Ancestry-specific effects of APOE on AD endophenotypes and risk factors

How does genetic ancestry influence risk for Alzheimer’s?

Shea J. Andrews, Ph.D.
Icahn School of Medicine at Mount Sinai
New York, NY - United States


According to the 2022 Alzheimer’s Association Facts and Figures, older non-Hispanic Blacks and Hispanic Americans are disproportionately more likely to have Alzheimer’s or other dementia. Understanding the factors that impact risk of later life memory changes in older non-Hispanic Blacks and Hispanic Americans is important to help reduce the risk of developing memory impairments later in life.

Much of what is known about Alzheimer’s genetic risk comes from studies of individuals with European ancestry. Because the genetic code (DNA) varies between individuals with different ancestries, the current findings may not translate to everyone. For example, a well-known risk variant called APOE e4 increases risk in certain populations, but recent work suggests it does not have the same effect on older Black/African American individuals. In addition to APOE e4, there are two other common variants of APOE including APOE e2 which has been shown to be protective against Alzheimer’s in some populations, and APOE e3 which is not associated with either increased or decreased risk. Exploring the impact of APOE-e4 genetic variation on Alzheimer’s risk in diverse populations is necessary to understand how ancestry influences genetic risk.

Research Plan

For this study, Dr. Shea Andrews will use samples collected from the Health and Aging Brain Study – Health Disparities (HABS-HD) which contains information from 3000 participants, including 1,000 non-Hispanic Whites, 1,000 Mexican Americans, and 1,000 African Americans. As part of the HABS-HD study, volunteers participated in cognitive testing, brain scan imaging, and blood samples collection. Using data from these participants, Dr. Andrews and team will explore whether genetic ancestry impacts the effect of APOE-e4 in Alzheimer’s risk, as well as on Alzheimer’s-related brain changes. They will examine the extent to which APOE-e4’s risk depends on the amount of genetic variation found across each person’s DNA related to their ancestry. Finally, the researchers will also explore whether APOE influences other risk factors for Alzheimer’s, such as levels of fats in the blood (cholesterol), body mass index, or diabetes.


This research hopes to understand how ancestry may influence the risk of Alzheimer’s in different populations and may uncover potential new mediators of disease risk.

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