Aging populations worldwide, particularly in developed countries, face an increasing burden of neurodegenerative diseases. The most common neurodegenerative disease is Alzheimer disease (AD), which is characterized by protein misfolding and aggregation. One intriguing characteristic is the broad spectrum of age at onset, even within specific risk groups (i.e, mutation carriers). Furthermore, the existence of resilient individuals (individuals who are positive for known biomarkers or have a high burden of genetic risk variants but do not exhibit symptoms), suggests that there are protective and disease-modifying genetic factors. The goal of this Project is to identify variants and genes that confer resilience as well as novel protective and modifying factors. We will use genetic data (GWAS, Exome-chip, Whole Exome Sequencing and Whole Genome Sequencing) from resilient individuals and compare them with matched affected individuals to identify protective and modifying genetic factors. The multi-factorial etiology and heterogeneity of AD may reveal itself in racial or ethnic differences in overall AD risk and in putative risk or protective factors or in the progression of neuropathology. For this reason, we will also determine if the modifier and protective variants, genes and pathways also play a role in other races, especially in African Americans.

Public Health Relevance

Aging populations worldwide, particularly in developed countries, face an increasing burden of neurodegenerative diseases, especially Alzheimer disease (AD). The goal of this study is to identify variants and genes that confer resilience as well as novel protective and modifying factors. Identifying protective variants, genes and pathways will be tremendously important for the neurodegenerative field; it will aid our understanding of the biology of the disease and, more importantly, to identify potential novel therapeutic targets.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Program Projects (P01)
Project #
2P01AG003991-36
Application #
9630145
Study Section
Special Emphasis Panel (ZAG1)
Project Start
Project End
Budget Start
2019-05-01
Budget End
2020-04-30
Support Year
36
Fiscal Year
2019
Total Cost
Indirect Cost
Name
Washington University
Department
Type
DUNS #
068552207
City
Saint Louis
State
MO
Country
United States
Zip Code
63130
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