| Title: | Dissecting Genetic and Non-Genetic Heterogeneity in Predisposition to Alzheimer's Disease and Vascular Traits in Pleiotropic Context |
| Lead Institution: | Duke University |
| Principal investigator: | Professor Alexander Kulminski |
Application 62778
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About
Increasing population of the elderly individuals worldwide raises serious concerns about burden of geriatric conditions in future, especially Alzheimer's disease, cardiovascular diseases, and other common aging-related diseases. These diseases can cluster in families suggesting that they can have genetic origin. Understanding their genetic origin could lead to breakthrough in preventing or curing such diseases. Despite continuing efforts, understanding their genetic basis remains very limited. Particular problem is to better understand genetic basis of Alzheimer's disease, its relationship to other aging-related diseases, and identify genetic variants which could help protect against such diseases. This project focuses on identifying personalized genetic profiles of risk and resilience to Alzheimer's disease and vascular diseases. This project includes four aims. In Aim 1, we plan to identify genetic variants which can be involved in regulation of Alzheimer's disease or vascular traits separately or combined in populations of different ancestries including Caucasians, African Americans, and Hispanics. In Aim 2, we will examine complexity in genetic predisposition to these diseases. These analyses will focus on complex structures of genes and chromosomal region and they will identify the differences in these structures in people with and without diseases. In Aim 3, we will perform analyses aimed to identify profiles of people who can be at larger and smaller risk of Alzheimer's and vascular diseases. These profiles will include genetic markers and the disease risk factors. In Aim 4, we will perform comprehensive bioinformatics analyses to examine potential molecular mechanisms of Alzheimer's and vascular diseases. Scientific rationale of our approach is based on core principles of evolutionary biology in genetics of diseases in the elderly which are characteristic of post-reproductive life. This rationale suggests that genetic predisposition to such diseases should be inherently complex and context specific, i.e., people can develop Alzheimer's and vascular diseases just because they have specific complex genetic profile tailored to a specific set of risk factors. This project is sponsored by the National Institute on Aging from the National Institutes of Health and it is funded for five years. This research will facilitate the development of interventional strategies aiming to promote healthy aging. It opens an avenue for developing interventions to prevent Alzheimer's and vascular diseases just by changing, for example, life style.2 Publications
| Pub ID | Title | Author(s) | Year | Journal |
|---|---|---|---|---|
| 9718 | Interaction Analysis Reveals Complex Genetic Associations with Alzheimer's Disease in the CLU and ABCA7 Gene Regions | Alireza Nazarian (+3) | 2023 | Genes |
| 12690 | Protective association of the ε2/ε3 heterozygote with Alzheimer's disease is strengthened by TOMM40-APOE variants in men | Alexander M. Kulminski (+4) | 2021 | Alzheimer's & Dementia |
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