Mapping polygenic risk scores to brain cells: insights for neurodegenerative diseases

Neurodegenerative diseases (NDDs) are driven by multiple related yet distinct pathological processes that evolve over decades, resulting in substantial clinical and neuropathological heterogeneity. Postmortem examinations of older individuals frequently reveal multiple coexisting neuropathologies, however, the underlying pathological processes cannot be easily assessed directly in living individuals. To quantify pathology-specific genetic signatures, we analysed a spectrum of NDDs using polygenic risk scores (PRSs) in the UK Biobank, restricting analyses to genes reported to be expressed in ma

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