2023 Sex and Gender in Alzheimer’s (SAGA) Grant (SAGA)
Leveraging Alzheimer’s clinical trials datasets to examine sex differences
Do genetics play a role in why women are at higher risk of Alzheimer’s?
Judy Pa, Ph.D.
University of California, San Diego
San Diego , CA - United States
Background
According to the 2023 Alzheimer’s Association Facts & Figures report, of the more than 6.5 million Americans with Alzheimer’s, nearly two-thirds are women. One gene that involved in Alzheimer’s is called apolipoprotein E (APOE), which provides instructions for making ApoE, a protein believed to help carry fats throughout the body. There are several genetic variations of APOE, including APOE-e2, APOE-e3 and APOE-e4. Studies have shown that in some populations, individuals who possess APOE-e4 have an increased risk for developing Alzheimer’s, compared to individuals with other APOE variants.
Research by Dr. Judy Pa indicates that women APOE-e4 carriers are at an increased risk of Alzheimer’s between ages 65 and 75, suggesting a critical window of intervention. Lecanemab is an amyloid immunotherapy (antibody) that has shown beta-amyloid-clearing abilities in clinical trials and has been approved by the FDA. The results from this clinical trial also showed a striking sex difference: men showed a slowing of decline by 43% whereas women only showed a 12% slowing of decline. In the trial, individuals who did not have APOE-e4 genes demonstrated more benefit than those who did.
Research Plan
Dr. Judy Pa plans to use data from the Alzheimer’s Disease Cooperative Study (ADCS). The ADCS has data from fourteen clinical trials that include cognitive data, genetic data, and in some cases brain scans and biological markers from blood and cerebrospinal fluid (CSF, the biological fluid surrounding the brain and spinal cord)(. By analyzing that data, they will assess the interaction between sex and gender on cognitive and functional outcomes. They will also examine the relationship between sex/gender on the brain scans and fluid biomarkers. Finally, they will analyze the three-way interaction between sex/gender and APOE-e4 status on cognitive outcomes.
Impact
The results of this study may help understand why women are at greater risk of Alzheimer’s than men, and if certain genes underlie women’s risk.