Plasma p-tau217 and Aβ42/40 as markers of Aβ pathology in the Lewy body continuum

초록

INTRODUCTION This study evaluated whether plasma phosphorylated tau-217 (p-tau217), amyloid beta (A beta)42/40, and their combination could serve as biomarkers of A beta co-pathology across the Lewy body continuum, where A beta is frequently observed from prodromal to symptomatic stages.METHODS Individuals with dementia with Lewy bodies (DLB), Parkinson's disease (PD), and their shared prodromal stage, isolated rapid eye movement (REM) sleep behavior disorder (iRBD) underwent plasma sampling, A beta-PET, and cognitive testing.RESULTS Higher plasma p-tau217, lower A beta 42/40, and their interaction were associated with greater A beta-PET uptake. Individuals with higher-than-median p-tau217 and lower-than-median A beta 42/40 showed the highest A beta burden. Both biomarkers predicted A beta-PET positivity, but only p-tau217 correlated with cognition. Among 44 iRBD participants followed prospectively, elevated baseline p-tau217 predicted phenoconversion to overt Lewy body disease.DISCUSSION Plasma p-tau217 and A beta 42/40 may serve as accessible biomarkers of cerebral A beta pathology and help identify individuals across the Lewy body continuum who could benefit from A beta-targeted therapy.Highlights Plasma phosphorylated tau-217 (p-tau217) and amyloid beta (A beta)42/40 predict cerebral A beta burden in the Lewy body continuum. Both biomarkers individually show high accuracy for identifying A beta positron emission tomography positivity. Plasma p-tau217, but not A beta 42/40, is associated with cognitive performance. Elevated plasma p-tau217 predicts future phenoconversion in isolated rapid eye movement sleep behavior disorder.

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