Timing of Changes in Alzheimer's Disease Plasma Biomarkers as Assessed by Amyloid and Tau PET Clocks

Jun 20, 2025Annals of neurology

Timing of Changes in Blood Markers of Alzheimer's Disease Compared to Brain Amyloid and Tau Levels

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Abstract

All 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.
  • Plasma GFAP became abnormal early in the tau PET timeline.
  • Plasma Aβ42/Aβ40 levels plateaued, while p-tau217, p-tau181, GFAP, and NfL levels increased throughout the modeled disease progression.
  • Variations in the timing of biomarker changes were observed across different assay platforms.

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Key numbers

7.9 years
Early Abnormality Timing for Aβ42/Aβ40
Time before amyloid PET positivity threshold.
73.7 years
Estimated Age at Tau PET Positivity
Mean age at which tau PET positivity was observed.
81.0 years
Estimated Age at Symptom Onset
Mean age at first clinical assessment indicating symptoms.

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