Accuracy of plasma biomarkers to detect Alzheimer's disease proteinopathy prior to dementia

INTRODUCTION: Plasma biomarkers sensitive to Alzheimer's disease (AD) proteinopathy prior to the onset of dementia have significant implications for early detection. METHODS: N Diagnostics' mass spectrometry (MS)-based plasma biomarkers (amyloid beta 42/40, %phosphorylated tau p-tau181, and %p-tau217) and amyloid probability scores (APS, PrecivityAD and APS2, PrecivityAD2) are associated with brain amyloid, brain tau, or preclinical cognitive decline. RESULTS: In this cohort study, %p-tau217 and the APS2 had high discriminative accuracy (area under the curve > 0.93) for identifying elevated brain amyloid and tau and were associated with faster preclinical cognitive decline. Using %p-tau217 or the APS2 in a theoretical AD trial screening scenario reduced amyloid positron emission tomography imaging costs up to 41% or 45%, respectively. DISCUSSION: N Diagnostics' MS-based plasma biomarkers can detect brain amyloid and tau with high accuracy prior to dementia and could aid in identifying candidates for clinical trials or therapeutic intervention. HIGHLIGHTS: N Diagnostics PrecivityAD2 (APS2) were concordant with amyloid and tau positron emission tomography status. Plasma %p-tau217 and the APS2 were associated with preclinical cognitive decline.