Stem Cell Bank Targets Alzheimer’s Genetic Risk
New stem cell platform models Alzheimer's risk using cells from people with high and low genetic predisposition.
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Researchers at the UK Dementia Research Institute at Cardiff University have developed a new stem cell resource that aims to improve understanding of how genetic factors influence the risk of Alzheimer’s disease (AD). The platform, built using blood cells from over 100 individuals with very high or low polygenic risk scores (PRS), is intended to support global research into the cellular mechanisms that contribute to the disease.
Polygenic risk score (PRS)
A numerical estimate of an individual’s genetic predisposition to a disease, calculated by combining the effects of multiple genetic variants identified through genome-wide association studies.
A focus on genetic extremes in Alzheimer’s risk
Alzheimer’s disease is one of the most common neurodegenerative disorders, affecting approximately 10% of people aged over 65 and nearly 1 in 3 individuals over 85. Both environmental and genetic factors contribute to disease risk. Recent advances in genome sequencing have identified many genetic variants that increase the likelihood of developing AD. The combined effect of these variants can now be used to calculate an individual’s PRS, a cumulative score that estimates their genetic predisposition to the disease.
Genetic variants
Small changes in the DNA sequence that can influence traits or disease risk.In this new study, published in Stem Cell Reports, the researchers selected donors based on the extremes of their AD PRS. About two-thirds of the 100 participants had been diagnosed with Alzheimer’s and had a high PRS. The remaining participants were age-matched, cognitively healthy individuals with low PRS.
Creating a stem cell bank to investigate disease mechanisms
Blood cells from each donor were reprogrammed into induced pluripotent stem cells (iPSCs), which can be used to generate many different cell types, including neurons. The resulting resource, called the iPSC Platform to Model Alzheimer’s Disease Risk (IPMAR), is the first of its kind created from individuals selected based on their genetic risk.
Induced pluripotent stem cells (iPSCs)
Adult cells, such as blood or skin cells, that have been genetically reprogrammed to return to an immature state, allowing them to differentiate into nearly any cell type in the body.Because iPSCs can be differentiated into specific brain cell types in the laboratory, IPMAR provides a system for directly studying the effect of AD-associated risk variants on cell health and function. This is a significant step towards mapping how combinations of genetic factors may drive neurodegenerative processes in different individuals.
Open access for global research use
The IPMAR platform will be made available to researchers worldwide. By enabling studies that compare brain cells derived from individuals with high and low PRS, scientists can begin to uncover the cellular mechanisms by which risk variants affect disease development. The researchers suggest that the platform could eventually support efforts to design personalised prevention or treatment strategies, though the current study does not explore therapeutic applications.
Reference: Maguire E, Winston J, Ellwood SH, et al. Modeling common Alzheimer’s disease with high and low polygenic risk in human iPSC: A large-scale research resource. Stem Cell Rep. 2025:102570. doi: 10.1016/j.stemcr.2025.102570
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