Alzheimer's Imaging Consortium.

Area of Science:

• Neurology
• Biomarker Discovery
• Alzheimer's Disease Research

Background:

• Plasma biomarkers like p-tau217 correlate strongly with amyloid-beta positron emission tomography (Aβ-PET) load.
• Longitudinal assessment of these biomarkers is crucial for clinical application and trial evaluation.

Purpose of the Study:

• To evaluate longitudinal changes in plasma biomarkers.
• To assess associations between these changes and subsequent Aβ-PET status.

Main Methods:

• Utilized data from 386 participants in the ADNI FNIH consortium over 11 years.
• Analyzed longitudinal trajectories of 5 p-tau217 and 4 Aβ42/40 assays with multiple Aβ-PET scans.
• Employed Cox proportional-hazard models to link baseline and longitudinal biomarker data to Aβ-PET positivity progression.

Main Results:

• Plasma p-tau217 assays, unlike Aβ42/40 assays, showed increases over time in both Aβ-PET negative and positive groups.
• Higher rate of change in plasma p-tau217 was associated with increased risk of progression to Aβ-PET positivity in Aβ-negative individuals.
• Rate of change in p-tau217 was a stronger predictor of future Aβ-PET positivity than baseline levels.

Conclusions:

• Plasma p-tau217 levels demonstrate longitudinal changes, while Aβ42/40 assays do not.
• The rate of change in plasma p-tau217 is the most potent predictor of future Aβ-PET positivity among individuals initially Aβ-negative.