Longitudinal changes in Alzheimer's-related plasma biomarkers and brain amyloid

Abstract

INTRODUCTION: Understanding longitudinal plasma biomarker trajectories relative to brain amyloid changes can help devise Alzheimer's progression assessment strategies. METHODS: We examined the temporal order of changes in plasma amyloid-β ratio ((Figure presented.)), glial fibrillary acidic protein (GFAP), neurofilament light chain (NfL), and phosphorylated tau ratios ((Figure presented.), (Figure presented.)) relative to 11C-Pittsburgh compound B (PiB) positron emission tomography (PET) cortical amyloid burden (PiB−/+). Participants (n = 199) were cognitively normal at index visit with a median 6.1-year follow-up. RESULTS: PiB groups exhibited different rates of longitudinal change in (Figure presented.). Change in brain amyloid correlated with change in GFAP (r = 0.5, 95% CI = [0.26, 0.68]). The greatest relative decline in (Figure presented.) (−1%/year) preceded brain amyloid positivity by 41 years (95% CI = [32, 53]). DISCUSSION: Plasma (Figure presented.) may begin declining decades prior to brain amyloid accumulation, whereas p-tau ratios, GFAP, and NfL increase closer in time. HIGHLIGHTS Plasma (Figure presented.) declines over time among PiB− but does not change among PiB+. Phosphorylated-tau to Aβ42 ratios increase over time among PiB+ but do not change among PiB−. Rate of change in brain amyloid is correlated with change in GFAP and neurofilament light chain. The greatest decline in (Figure presented.) may precede brain amyloid positivity by decades.