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

Understanding longitudinal plasma biomarker trajectories relative to brain amyloid changes can help devise Alzheimer's progression assessment strategies.

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.

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]).

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.