2022 Alzheimer’s Association Investigator Initiated Award (AAIIA)
Sex-Dependent Genetic Landscape of Late-Onset Alzheimer's Disease
How might genetic differences between men and women impact Alzheimer’s risk?
Ornit Chiba-Falek, Ph.D.
Duke University School of Medicine
Durham, NC - United States
Background
Genes play an important role in Alzheimer’s. For most individuals who have late-onset Alzheimer’s, the genetic mechanisms are complicated and not fully understood. The most prominent genetic variation thought to increase risk in some populations for late-onset Alzheimer’s is APOE-e4, a gene variation that provides instructions for making ApoE protein. However, there are also many other genetic variations that likely impact Alzheimer’s risk, many of which have not been identified.
In addition to studying specific genes that increase risk, researchers also investigate biological mechanisms by which genes can be changed or activated (turned ‘on’). For example, researchers study the epigenome or transcriptome to understand biological mechanisms by which genes may be regulated. The epigenome is a record of chemical modifications that can turn genes “on” or “off” in response to environment or disease state. The transcriptome is the complete instructions for which genes should be turned “on” and “off” within that cell in response to the environment or disease state.
According to the 2022 Alzheimer’s Association Facts and Figures report, almost two-thirds of Americans with Alzheimer’s are women. Yet, little is known about how sex may impact epigenomics and transcriptomics and contribute to differences in genetic risk of Alzheimer’s.
Research Plan
Dr. Ornit Chiba-Falek and colleagues will study the brains of individuals who have Alzheimer’s using a sophisticated, newly developed technique that can analyze the genes in individual cells in multiple ways at the same time. This technique can study a cell’s transcriptome and its epigenome. The researchers will analyze the samples for differences between men and women.
Impact
Results from this project may shed new light on the role of genetics in Alzheimer’s. The findings may also lead to novel methods of identifying disease risk genes and other biological mechanisms behind Alzheimer’s.