2023 Alzheimer's Association Research Grant (AARG)

Genomic Admixture Effects on Neuropathology and Cognition: APOE and Beyond

What genetic factors impact Alzheimer’s-related brain changes in diverse populations?

Michel Naslavsky, Ph.D.
University of Sao Paulo
São Paulo, Brazil

Background

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, the apolipoprotein E (APOE) gene provides instructions for making the ApoE protein that is thought to help carry fats throughout the body. There are several variations of the APOE gene, including APOE-e2, APOE-e3 and APOE-e4. The APOE e4 variation increases risk of Alzheimer’s in certain populations, but recent work suggests it does not have the same effect on older Black/African American individuals. In contrast to APOE-e4, APOE-e2 has been shown to be protective against Alzheimer’s in some populations. APOE-e3 is not associated with either increased or decreased risk. Exploring the impact of genetic variation on Alzheimer’s risk in diverse populations is necessary to understand how ancestry influences genetic risk.

Research Plan

Dr. Michel Naslavsky and colleagues will study the genetic factors that interact with the APOE gene to impact Alzheimer’s-related brain and behavior changes in individuals with non-European ancestry. The researchers will use DNA samples from the Biobank for Aging Studies at the University of São Paulo Medical School in Brazil. These samples come from individuals aged 50 years and older with diverse genetic ancestry, including European, African, and Native American. The researchers will conduct whole genome sequencing studies (analyses that reveal the complete genetic makeup of an individual) on DNA samples from individuals with Alzheimer’s-associated brain changes and those without.

Impact

This research hopes to understand how ancestry may influence the risk of Alzheimer’s in different populations and may reveal how different genetic factors interact to impact disease risk.