Long-Term Changes in Blood Biomarkers Associated with Brain White Matter Injury

The goal of this study is to determine whether myelin dysfunction contributes to white matter hyperintensities severity through proteomic mechanisms reflected by longitudinal changes in myelin-related proteins and plasma Alzheimer’s disease and neurodegenerative biomarkers.

White matter hyperintensities (WMH) are spots seen on brain scans that raise the risk for memory loss, stroke, and dementia, but we do not yet know why they form. This study will follow blood markers of myelin, the protective coating of brain, along with Alzheimer’s-related proteins over 15 years in African American older adults from the place with the 5th highest dementia prevalence in the United States, Jackson, Mississippi. Results will show whether these blood markers can predict WMH and point to their biological origins.

This project is innovative because it will establish the temporal ordering between longitudinal myelin-related proteomic changes, Alzheimer’s disease biomarker elevations, and white matter injury in African American adults, a population historically underrepresented in aging research. The study integrates 3 waves of high-dimensional plasma proteomics spanning ~15 years with longitudinal Alzheimer’s disease biomarkers and neuroimaging in the Jackson Heart Study. Additionally, biomarkers will be harmonized with major national cohorts using shared laboratory protocols, enhancing reproducibility and future cross-cohort meta-analytic opportunities.

This study will provide new insight into the biological mechanisms driving white matter injury and brain aging, potentially identifying early blood-based markers and therapeutic targets before substantial brain damage occurs. Findings may improve prevention and risk stratification strategies for vascular and Alzheimer’s disease-related cognitive decline, particularly in African American adults who experience a disproportionately high burden of these conditions.