Cross Sectional and Longitudinal Racial Disparity in Molecular Biomarkers of Alzheimer Disease

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Currently, almost all molecular biomarker studies in Alzheimer disease (AD) and clinical trials on AD have been largely limited to Caucasian participants. The fundamental question is whether AD, as currently defined, is the same disease for African Americans, the largest under-represented group (URG) in the US, and Caucasians, both in the preclinical and symptomatic stages. Conflicting results have thus far appeared in the literature about this very question, largely due to the limited sample sizes of African Americans in published studies. We propose to tackle these problems by implementing a multi-center and longitudinal study with a central and standardized re-processing of all currently existing and prospectively collected cerebrospinal fluid (CSF) samples, magnetic resonance imaging (MRI) structural scans, and positron emission tomography (PET) beta-amyloid and PET tau imaging scans, in addition to a harmonization of clinical and cognitive outcomes. We will join forces with five major biomarker studies of AD: the Washington University Knight Alzheimer Disease Research Center (ADRC), University of Pennsylvania AD Core Center, Emory University ADRC, Harvard Aging Brain Study, and the Anti- Amyloid Treatment in Asymptomatic Alzheimer's trial. We will assemble likely the largest biomarker data set of African Americans, and analyze resulting AD biomarker and cognitive data in a comprehensive manner to examine the racial disparity in both the preclinical and the symptomatic stages. We will further assess the roles that AD risk factors, APOE ε4 status, family history, age, sex, education, socioeconomic status, and vascular burden play in cross sectional and longitudinal differences between African Americans and Caucasians. We will also determine the racial differences in the predictability of AD biomarkers to concurrent and longitudinal cognitive outcomes. These racial differences, if confirmed by the proposed study on the largest African Americans biomarker cohort, may imply potentially differential treatment responses between the races, and hence will have profound implications to the design and analyses of ongoing and future prevention and treatment trials of AD.