Biological variation estimates of Alzheimer’s disease plasma biomarkers in healthy individuals

Abstract

INTRODUCTION: Blood biomarkers have proven useful in Alzheimer’s disease (AD) research.However,littleisknownabouttheirbiologicalvariation(BV),whichimproves theinterpretation of individual-level data. METHODS: Wemeasuredplasmaamyloid beta (Aβ42, Aβ40), phosphorylated tau (p tau181, p-tau217, p-tau231), glial fibrillary acidic protein (GFAP), and neurofilament light chain (NfL) in plasma samples collected weekly over 10 weeks from 20 partici pantsaged40to60yearsfromtheEuropeanBiologicalVariationStudy.Weestimated within-(CVI)andbetween-subject(CVG)BV,analyticalvariation,andreferencechange values (RCV). RESULTS: Biomarkers presented considerable variability in CVI and CVG.Aβ42/Aβ40 hadthelowestCVI (≈3%)andp-tau181thehighest(≈16%), whileothersrangedfrom 6%to10%.MostRCVsrangedfrom20%to30%(decrease)and25%to40%(increase). DISCUSSION: BV estimates for AD plasma biomarkers can potentially refine their clinical and research interpretation. RCVs might be useful for detecting significant changes between serial measurements when monitoring early disease progression or interventions.