Tuesday, April 1, 2025
4/1/2025
Proteomic biomarkers of incident cognitive impairment in Black and White adults - Project Summary Black adults in the U.S. have a disproportionately higher risk of Alzheimer’s disease and related dementias (ADRD) compared with non-Hispanic White adults. Disparities in cardiometabolic risk factors and diseases and social determinants of health (such as educational access, stress due to discrimination, neighborhood factors, and others) likely contribute to this disparity, but exact mechanisms are unknown. We hypothesize that inflammation may be a key feature linking cardiometabolic and social determinants of health disparities with the risk of incident cognitive impairment and dementia. We propose to test this hypothesis through systemic analysis of the circulating proteome with risk of incident cognitive impairment and trajectories of cognitive function in a large biracial population from the REasons for Geographic and Racial Differences in Stroke (REGARDS) study. REGARDS is a longitudinal cohort of 30,239 non-Hispanic Black and White adults across the contiguous U.S. with pre-existing genome-wide genotyping data and rich cardiovascular and neurocognitive phenotyping. We will assess 3,072 circulating plasma proteins (including >700 inflammation related proteins) for associations with risk factors for cognitive impairment, including age, social determinants of health, and cardiometabolic risk factors, and with incident cognitive impairment and trajectories of cognitive function over >17 years of follow-up. Differences in levels of identified proteomic biomarkers by race and sex will be assessed. Finally, we will integrate available genome-wide genotyping data and the plasma protein data newly generated in this study to determine if the protein data can elucidate mechanisms underlying associations of previously identified genetic variants with dementia-related phenotypes. We hypothesize this work will identify non-invasive protein biomarkers of cognitive impairment and ADRD, including risk biomarkers which may have adverse levels in Black compared with White adults. This study is responsive to PAR-22-093 (NOT-AG-21-033: Health Disparities and Alzheimer’s Disease), assessing biological pathways that may contribute to racial disparities in ADRD risk and related to NIA AD+ADRD Research Implementation Milestone 1.I. The proteomic data generated in this study will be made widely available to the scientific community through appropriate public repositories (such as dbGaP). Results from this study may improve ADRD risk prediction, elucidate biological mechanisms of ADRD, and improve understanding of factors that contribute to ADRD health disparities.
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