Modeling common Alzheimer's disease with high and low polygenic risk in human iPSC: A large-scale research resource

Maguire, Emily, Winston, Jincy, Ellwood, Sarah H., O'Donoghue, Rachel, Shaw, Bethany, Morales, Atahualpa Castillo, Keat, Samuel, Evans, Alexandra, Marshall, Rachel, Luckcuck, Lauren, Brown, Laura, Salis, Elisa, Leonenko, Ganna ORCID: https://orcid.org/0000-0001-8025-661X, Denning, Nicola, Allen, Nicholas D. ORCID: https://orcid.org/0000-0003-4009-186X, Escott-Price, Valentina ORCID: https://orcid.org/0000-0003-1784-5483, Webber, Caleb ORCID: https://orcid.org/0000-0001-8063-7674, Taylor, Philip R. ORCID: https://orcid.org/0000-0003-0163-1421, Sims, Rebecca ORCID: https://orcid.org/0000-0002-3885-1199, Cowley, Sally A., Williams, Julie ORCID: https://orcid.org/0000-0002-4069-0259, Carpanini, Sarah M. and Hall-Roberts, Hazel 2025. Modeling common Alzheimer's disease with high and low polygenic risk in human iPSC: A large-scale research resource. Stem Cell Reports 20 , 102570. 10.1016/j.stemcr.2025.102570

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Abstract

Common forms of Alzheimer’s disease (AD) are complex and polygenic. We have created a research resource that seeks to capture the extremes of polygenic risk in a collection of human induced pluripotent stem cell (iPSC) lines from over 100 donors: the IPMAR Resource (iPSC Platform to Model Alzheimer's Disease Risk). Donors were selected from a large UK cohort of 6,000+ research-diagnosed early or late-onset AD cases and elderly cognitively healthy controls, many of whom have lived through the age of risk for disease development (>85 years). We include iPSC with extremes of global AD polygenic risk (high-risk late-onset AD: 34; high-risk early-onset AD: 29; low-risk control: 27) as well as those reflecting complement pathway-specific genetic risk (high-risk AD: 9; low-risk controls: 10). All iPSC have associated clinical, longitudinal, and genetic datasets and will be available through collaboration or from cell (EBiSC) and data (DPUK) repositories.

Item Type:	Article
Date Type:	Publication
Status:	In Press
Schools:	Schools > Medicine
Publisher:	Cell Press
ISSN:	2213-6711
Date of First Compliant Deposit:	15 July 2025
Date of Acceptance:	5 June 2025
Last Modified:	17 Jul 2025 11:15
URI:	https://orca.cardiff.ac.uk/id/eprint/179794

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