<< Back

2020 Alzheimer's Association Research Fellowship (AARF)

Putting the Pieces Together: APOE, Age, Sex, and Ancestry in AD Genetics

How may an individual’s genetic risk for Alzheimer’s be impacted by a variety of genetic and non-genetic factors?

Michaël Belloy, Ph.D.
Stanford University
Redwood City, CA - United States


The apolipoprotein E (APOE) gene provides instructions for making the ApoE protein that is thought to help carry fats throughout the body. Each person has two copies of APOE in their DNA. There are several variations of the APOE gene including APOE-e2, APOE-e3 and APOE-e4. Possessing APOE-e4 compared to the other variations is thought to impact a person’s risk of developing Alzheimer’s in some populations and this risk is further increased in an individual who has two copies of APOE-e4. 

Dr. Michael Belloy believes that additional factors, such as age, sex and ancestry, may impact the chances of developing Alzheimer’s in an individual with the APOE-e4 genetic variation.

Research Plan

Dr. Belloy and colleagues will study how an individual’s genetic risk for Alzheimer’s may be impacted by a variety of genetic and non-genetic factors. The researchers will conduct several genetic analyses of nearly 500,000 people with and without APOE-e4 in the United Kingdom. The researchers will leverage genetic data from the UK Biobank, a large study of genetics and disease in the United Kingdom. 

The researchers will first look for genes throughout the entire genome (a person’s complete set of genes) that may be associated with Alzheimer’s risk. Dr. Belloy’s team will then analyze these datasets to study how the presence of these risk genes may be impacted by age, sex or personal ancestry. Furthermore, the researchers will look for dementia risk genes that are associated with a person’s sex (male versus female). 

Finally, the researchers will further analyze their genetic data to determine how certain genes may impact biological markers of Alzheimer’s. This will include analyzing cerebrospinal fluid (or CSF, the biological fluid surrounding the brain and spinal cord) for abnormal protein levels including beta-amyloid and tau which could accumulate to form plaques and tangles, two hallmark brain changes observed in Alzheimer’s.


The study results could offer insights into how the interplay between various factors including risk genes, age, sex and ancestry among others may impact Alzheimer’s and other dementia.

Back to Top