Traumatic Brain Injury and Alzheimer's Disease
Abstract
There is growing evidence that individuals with TBI are at increased risk for AD/ADRD. However, TBI survivors don't invariably develop dementia in life and patients with dementia usually don't have a history of head injury indicating that more work is needed to understand the relationship between TBI andAD/ADRD. Beyond the E4 allele of apolipoprotein E (APOE E4), we have integrated common genetic variants into a polygenic hazard score (PHS) for predicting AD dementia age of onset. Among APOE E3/3 cognitively normal individuals, who constitute the majority of all US individuals with AD, Alzheimer's Disease PHS (adPHS) predicts a) longitudinal cognitive decline and b) amyloid and tau pathology. Integrating common genetic variants jointly associated with vascular risk factors and AD, we have recently developed a vascularPHS (vPHS) to identify people who may be at high risk for both vascular and Alzheimer's pathology. In this proposal, our objective is to examine whether adPHS and vPHS predict cognitive decline, vascular and AD pathology among non-demented individuals with a history of TBI. By using two different polygenic scores, we will evaluate the unique contribution of Alzheimer's and vascular associated pathways to TBI. We hypothesize that among people with high genetic risk, TBI will accelerate Alzheimer's neurodegeneration, directly or through vascular disease.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jan 01, 2023
- Accession Number
- AD1217422
Entities
People
- Jennifer S. Yokoyama
- William G. Mantyh
Organizations
- University of California Regents