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 Aβ₄₂/Aβ₄₀, glial fibrillary acidic protein (GFAP), neurofilament light chain (NfL), and phosphorylated tau ratios (p-tau181/Aβ₄₂, p-tau231/Aβ₄₂) 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 Aβ₄₂/Aβ₄₀(β = 5.41 × 10⁻⁴, SE = 1.95 × 10⁻⁴, p = 0.0073). Change in brain amyloid correlated with change in GFAP (r = 0.5, 95% CI = [0.26, 0.68]). The greatest relative decline in Aβ₄₂/Aβ₄₀ (−1%/year) preceded brain amyloid positivity by 41 years (95% CI = [32, 53]).// Discussion: Plasma Aβ₄₂/Aβ₄₀ may begin declining decades prior to brain amyloid accumulation, whereas p-tau ratios, GFAP, and NfL increase closer in time./