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 (Aβ 42 /Aβ 40 ), glial fibrillary acidic protein (GFAP), neurofilament light chain (NfL), and phosphorylated tau ratios (p-tau181/Aβ 42 , p-tau231/Aβ 42 ) relative to 11 C-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 Aβ 42 /Aβ 40 (β = 5.41 × 10^ -4 , SE = 1.95 × 10 -4 , p = 0.0073). Change in brain amyloid was correlated with change in GFAP (r = 0.5, 95% CI = [0.26, 0.68]). Greatest relative decline in Aβ 42 /Aβ 40 (-1%/year) preceded brain amyloid positivity onset by 41 years (95% CI = [32, 53]).
Discussion: Plasma Aβ 42 /Aβ 40 may begin declining decades prior to brain amyloid accumulation, whereas p-tau ratios, GFAP, and NfL increase closer in time.