Core E: Biosample Core

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Biosample Core (E) Summary Significant advances have been made in the genetic risk factors for Alzheimer’s disease (AD), from identification of early onset familial mutations in the amyloid precursor protein and presenilin, to discovery of late onset Alzheimer’s disease risk alleles like APOE ε4 and over 30 loci through genome wide association studies. Similarly, the development of biomarkers for pathology, for beta-amyloid (Ab, A) and Tau (T) have advanced through detection by positive emission tomography (PET) and cerebrospinal fluid (CSF). Additional biomarkers of neurodegeneration (N), neurofilament light chain (NfL)- an astrogliosis marker and glial acidic fibrillary protein (GFAP) have increased the accuracy of diagnosis in early disease stages, or even prodromal to AD. Despite these advances, there still are major limitations to understanding and diagnosing AD. A major limitation of large cohort studies has been the under-representation of ethnic/racial minorities as most studies have evaluated predominantly homogenous cohorts of European ancestry. This does not reflect the cross ancestral diversity in the United States, Canada and globally. For example, the most robust late- onset Alzheimer’s disease risk variant, APOE ε4, confers a higher risk of disease in individuals of European ancestry than it does in Hispanics and African-Americans, particularly in carriers with only one APOE ε4 allele. Biomarkers that identify AD through PET imaging or lumbar puncture-acquired CSF are also limited due to the need for expensive technology or invasive procedures. Advancement of blood-based biomarkers offers promise of an accessible diagnostic tool to identify AD as early as possible. Establishing cohorts that investigate other groups, such as Asians in this study, is critical to understanding AD in ethnically and racially diverse countries like the United States and Canada. To address this gap in knowledge, the Asian Cohort for Alzheimer’s disease (ACAD) was established. The goal of this Core is to establish a biorepository of genetic data and blood samples from Asian populations for the investigation of AD. With over 5000 DNA samples and 3000 plasma and serum samples from elderly participants, it will be one of the largest collections in the world dedicated to Asian groups in North America. DNA will be stored and processed at NCRAD analyzed by the Center for Applied Genomics, with data accessible through NIAGADS. NCRAD will use Plasma to measure biomarkers for amyloid, tau, neurodegeneration. Analysis of genetic data and blood biomarkers will be done in Project 1 and 2 and compared to other datasets to identify Asian-specific genetic and biomarker profiles, genetic variants of interest, and thresholds for diagnostic detection of AD.