Blood Biomarker Development and Validation in Chronic Traumatic Encephalopathy and Alzheimer's Disease and Alzheimer's Disease Related Dementias

The project will leverage the Brain Donation Registry (BDR) hosted by the Concussion Legacy Foundation (CLF). It will recruit 1000 BDR individuals (800 with repetitive head impacts, 200 without; all 40+ years) to undergo phlebotomy at a Quest lab for blood banking at BioSEND. Clinical characterization will be performed using the UCSF-BU internet-based Brain Health Registry-Head Impact & Trauma Surveillance Study. Plasma biomarker analyses will be conducted on 300 of these individuals (200 RHI, 100 non-RHI), measuring six p-tau epitopes (181+199+202+205+217+231), Aβ40/42, total tau, glial fibrillary acidic protein, and neurofilament light. The same analytes will be measured in blood and brain for an expected 100 brain donations during the grant. Additionally, 120 brain donors from the BU ADRC bank with existing plasma biomarkers will be used as autopsy-proven AD and non-AD comparators. Aim 1 will compare plasma biomarkers between RHI and non-RHI groups and test plasma biomarker and clinical associations. Aim 2 will involve plasma-to-autopsy studies using the 100 BDR brain donations (enriched for CTE) and the 120 BU ADRC donors. Aim 3 will test RHI and plasma biomarker associations.