Timing of Changes in Alzheimer's Disease Plasma Biomarkers as Assessed by Amyloid and Tau PET Clocks.
Level 3 - non-randomized controlled study
Longitudinal cohort study modeling biomarker trajectories
PubMed 40539416 · doi:10.1002/ana.27285
What was done
Data from the Alzheimer's Disease Neuroimaging Initiative (ADNI), including 784 individuals with longitudinal amyloid PET and 359 with longitudinal tau PET, were analyzed to estimate age at PET positivity. Longitudinal plasma biomarker measurements (Aβ42/Aβ40, p-tau217, p-tau181, GFAP, and NfL across six assay platforms) were evaluated in subsets with estimated amyloid PET positivity age (n = 190) and tau PET positivity age (n = 70). Generalized Additive Mixed models were used to model biomarker trajectories relative to PET positivity timelines and estimated symptom onset age (calibrated in 17 clinical progressors) to identify when biomarkers crossed abnormality thresholds.
What was found
All plasma biomarkers except NfL became abnormal prior to established thresholds for amyloid and tau PET positivity. Plasma Aβ42/Aβ40 became abnormal very early in both amyloid and tau PET timelines and subsequently plateaued. Plasma GFAP became abnormal early in the tau PET timeline. Plasma p-tau217, p-tau181, GFAP, and NfL levels continuously increased throughout modeled disease progression. Variations in timing were observed across different assay platforms. Specific numerical values and time intervals were not reported in the abstract.
Why it matters
These findings suggest plasma Aβ42/Aβ40 is most useful for detecting early amyloid pathology, whereas p-tau variants, GFAP, and NfL are better suited for tracking and staging progressive disease.
Limits
Subsets with both longitudinal plasma and PET-estimated ages were small (n = 190 for amyloid, n = 70 for tau), and symptom onset estimation relied on only 17 clinical progressors. No quantitative effect sizes, time estimates, or confidence intervals were provided in the abstract.
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