Longitudinal changes in Alzheimer's related plasma biomarkers and brain amyloid
Published in Alzheimer's and Dementia, 2023
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.
Highlights:
- Plasma Aβ42/Aβ40 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 Aβ42/Aβ40 may precede brain amyloid positivity by decades.