National Centralized Repository for Alzheimer's Disease and Related Dementias (NCRAD)

Project Summary/Abstract This administrative supplement outlines the critical role of the National Centralized Repository for Alzheimer’s Disease and Related Dementias (NCRAD) in establishing a centralized, high-quality resource of induced pluripotent stem cells (iPSCs) developed as part of the U54 Centers funded under RFA-AG-040. As the prevalence of Alzheimer’s disease and related dementias (ADRD) continues to rise, understanding the complex genetics and pathophysiology of Alzheimer’s disease (AD) and ADRD is paramount. Animal models were the primary approach used for functional genomics; but with small effect risk loci and the difficulty of recapitulating AD in animal models, there is a new focus on cellular models. Induced pluripotent stem cells are of particular interest since they can differentiate into a variety of central and peripheral nervous system cell types. NCRAD has a proven track record in banking and distributing DNA samples that have facilitated significant genetic discoveries. As the field shifts towards cellular models, particularly iPSCs, NCRAD is uniquely positioned to serve as the central repository. This supplement proposes to standardize and centralize the collection, storage, and distribution of iPSCs generated by new U54-funded initiatives. Key innovations include NCRAD's existing expertise with iPSCs and its established infrastructure for integrating iPSCs with rich clinical data from studies like ADNI. The revised approach focuses on the following main aims: developing comprehensive standard operating procedures (SOPs) for both sample submission (Aim 1) and sample distribution (Aim 2). This includes creating detailed manuals of procedures, establishing robust data linking protocols with other repositories (e.g., AD Knowledge Portal, NIAGADs, LONI), and refining a review process for iPSC requests. Finally, Aim 3 addresses the operational implementation of these procedures for the efficient and standardized receipt of new iPSC resources. By centralizing this critical resource, NCRAD will significantly accelerate ADRD research, foster reproducibility, and facilitate the discovery of novel therapeutic targets.