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Alzheimer's & Dementia

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Alzheimer's disease, Medical research


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]). 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.


©2023 Alzheimer’s Association. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.



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