ArticleJournal of Alzheimer's disease : JAD2023
Testing a Polygenic Risk Score for Morphological Microglial Activation in Alzheimer's Disease and Aging.
Article in Journal of Alzheimer's disease : JAD, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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2 citing papers in PubMed, 1 citations in OpenAlex.
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6 authors at 3 institutions in 2 countries.
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Abstract
backgroundNeuroinflammation and the activation of microglial cells are among the earliest events in Alzheimer's disease (AD). However, direct observation of microglia in living people is not currently possible. Here, we indexed the heritable propensity for neuroinflammation with polygenic risk scores (PRS), using results from a recent genome-wide analysis of a validated post-mortem measure of morphological microglial activation.
objectiveWe sought to determine whether a PRS for microglial activation (PRSmic) could augment the predictive performance of existing AD PRSs for late-life cognitive impairment.
methodsFirst, PRSmic were calculated and optimized in a calibration cohort (Alzheimer's Disease Neuroimaging Initiative (ADNI), n = 450), with resampling. Second, predictive performance of optimal PRSmic was assessed in two independent, population-based cohorts (total n = 212,237). Finally, we explored associations of PRSmic with a comprehensive set of imaging and fluid AD biomarkers in ADNI.
resultsOur PRSmic showed no significant improvement in predictive power for either AD diagnosis or cognitive performance in either external cohort. Some nominal associations were found in ADNI, but with inconsistent effect directions.
conclusionWhile genetic scores capable of indexing risk for neuroinflammatory processes in aging are highly desirable, more well-powered genome-wide studies of microglial activation are required. Further, biobank-scale studies would benefit from phenotyping of proximal neuroinflammatory processes to improve the PRS development phase.
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