Center for Alzheimer's and Related Dementias: iPSCs to study APOE heterogeneity in Alzheimers disease and Alzheimers disease-related dementias (iDA)

National Institute On Aging

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Abstract

The iPSCs to study APOE heterogeneity in Alzheimer’s disease and Alzheimer’s disease-related dementias (iDA) project represents a collaborative effort between the NIH's Center for Alzheimer's and Related Dementias (CARD) and the Alzheimer's Disease Neuroimaging Initiative (ADNI). This initiative aims to generate 200 induced pluripotent stem cell (iPSC) lines from peripheral blood mononuclear cells obtained from Alzheimer's disease and related dementia patients as well as healthy controls. The project is currently on track with 169 iPSC lines completed as of this reporting period, with completion of all 200 lines estimated for early 2026. The project emphasizes covering common genotype combinations of the APOE gene, a key Alzheimer's disease genetic risk factor. These iPSC lines will undergo comprehensive quality control including whole genome sequencing, long-read sequencing, and array-based genotyping, followed by advanced characterization studies including single-cell RNA sequencing, ATAC sequencing, and imaging assays. The resource will be made publicly available through NCRAD to support the broader research community in advancing our understanding of Alzheimer's disease mechanisms, in ensuring rigor and reproducibility in human model systems, and in developing therapeutic or preventative interventions.