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

INTRODUCTION: Blood biomarkers have proven useful in Alzheimer's disease (AD) research. However, little is known about their biological variation (BV), which improves the interpretation of individual-level data.METHODS: We measured plasma amyloid beta (A beta 42, A beta 40), 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 participants aged 40 to 60 years from the European Biological Variation Study. We estimated within- (CVI) and between-subject (CVG) BV, analytical variation, and reference change values (RCV).RESULTS: Biomarkers presented considerable variability in CVI and CVG. A beta 42/A beta 40 had the lowest CVI (approximate to 3%) and p-tau181 the highest (approximate to 16%), while others ranged from 6% to 10%. Most RCVs ranged from 20% to 30% (decrease) and 25% to 40% (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.