Modeling common Alzheimer's disease with high and low polygenic risk in human iPSC: A large-scale research resource.
Maguire E., Winston J., Ellwood SH., O'Donoghue R., Shaw B., Morales AC., Keat S., Evans A., Marshall R., Luckcuck L., Brown L., Salis E., Leonenko G., Denning N., EADB consortium None., Allen ND., Escott-Price V., Webber C., Taylor PR., Sims R., Cowley SA., Williams J., Carpanini SM., Hall-Roberts H.
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.