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News
A new polygenic risk score (PRS) for Alzheimer's disease, built using data from over 63,000 cases across multiple ancestries, outperforms previous European-only models — especially for African American, Hispanic, and East Asian individuals. The score also links to early brain and cognitive changes, and hints at sex-specific differences. Published in Nature Genetics, it could reshape how we screen and select patients for prevention trials.
Researchers have developed a new multi-ancestry polygenic risk score (PRS) for Alzheimer's disease (AD) that significantly outperforms older models — which were built almost exclusively on data from people of European ancestry. The new PRS was trained on data from more than 63,000 AD cases and 484,000 age-matched controls spanning African American, Hispanic, East Asian, and European populations, then validated in two independent diverse cohorts. The result: better risk prediction across the board, with the biggest gains seen in historically underrepresented groups.
Beyond diagnosis prediction, the PRS also correlated with real-world biological and cognitive markers — including poorer memory and executive function, smaller hippocampal volume on MRI, and abnormal levels of amyloid-β and phosphorylated Tau in cerebrospinal fluid. Notably, women with high PRS showed greater Tau deviations, hinting at potential sex-specific risk pathways. Longitudinal data showed that individuals with the highest PRS experienced the steepest cognitive decline in the years leading up to AD onset.
Key Takeaways:
Why it matters: Most genetic risk tools for Alzheimer's were built on predominantly white datasets, leaving diverse populations underserved. This new PRS closes that gap — and its links to early biological changes mean it could one day guide personalized prevention, not just prediction.
