Administrative Core

Summary Abstract: “Centrally-linked Longitudinal pEripheral biomARkers of AD (CLEAR-AD) in multi-ethnic populations” is a collaborative U19 application of >40 experts from multiple disciplines, across 13 institutions leveraging 8 independent NIH-funded cohorts of >7,000 brain and >13,000 blood samples from >3,700 individuals, in which >20,000 multi-omics data points will be generated and integrated with >48,000 harmonized Alzheimer’s disease (AD) endophenotypes under this U19. Our goal is to discover, replicate and validate the next-generation of AD blood multi-omics biomarker candidates that represent molecular perturbation signatures in the brain which are reflected in antemortem neuroimaging/cerebrospinal fluid (CSF) and post-mortem neuropathology phenotypes of this complex disease. We aim to discover centrally-linked peripheral molecular signatures (CLPMS) that can serve as future centrally-linked peripheral biomarkers (CLPBM) through transcriptome, epigenome, proteome, metabolome/lipidome data generation, integration with existing other -omics data and analysis in matched postmortem brain:antemortem blood samples (Project 1=P1); and to characterize their longitudinal dynamic profiles in non-Hispanic white (NHW) and diverse, underrepresented populations (URP) of African American (AA) and Latino American (LA) participants (P2, P3). We expect to identify predictive, diagnostic, prognostic and therapeutic AD biomarkers with mechanistic insights; to enhance biomarker research in trial-ready multi-ethnic populations and to provide the research community with a vast resource of rigorously generated, replicated and validated multi-omics biomarkers. To achieve these aims, we will utilize and integrate existing and future data and biospecimens from Alzheimer’s Disease Neuroimaging Initiative (ADNI), Mayo Clinic Study of Aging (MCSA) and 6 AD Research Centers (ADRCs). The Administrative Core (Core 1: C1) will provide direction and oversight to the projects and cores of this program (C2. Omics and C3. Analytic Cores) and facilitate their execution. The Administrative Core will achieve the program goals through 1) integration of the participating institutions and studies; 2) execution of all regulatory activities; 3) establishing a Diversity Scholars Program for trainees from URPs; 4) enabling communication, outreach and knowledge sharing within the U19, with related programs, the whole research community and public stakeholders; and 5) ensuring rigor, reproducibility and transparency by making all data, algorithms, and outcomes available to the research community. The Specific Aims for the Administrative Core are: 1) To provide direction, oversight, integration and facilitate execution of all U19 aims under the leadership of its Steering Committee, External Advisory Board and NIH (1a); and to execute all regulatory activities for the program (1b). 2) To perform outreach and education by establishing a U19 Diversity Scholars Program to train AA and LA scientists (2a) and bi-annual meetings (2b). 3) To share data and knowledge in an open-science fashion on NIH approved repositories to promote transparency, reproducibility and reuse of all CLEAR-AD program assets.