Prognostic Value of Blood-Based P-Tau217 Levels for Progression to Cognitive Impairment

Buckley RF, Townsend DL, Birkenbihl CJ, Coughlan GT, Schultz AP, Donohue M, Aisen PS, Johnson KA, Sperling RA

1. 01

   Each 1-SD increase in baseline plasma p-tau217 was associated with progression to cognitive impairment (HR 1.38, 95% CI 1.30-1.46)

2. 02

   Association persisted after adjustment including amyloid-PET Centiloids (HR 1.32, 95% CI 1.24-1.41)

3. 03

   High p-tau217 (1.1-2.4 SD): 24% (95% CI 20-28%) absolute 5-year risk of progression

4. 04

   Very high p-tau217 (>2.5 SD): 38% (95% CI 33-43%) absolute 5-year risk of progression

5. 05

   Elevated p-tau217 also predicted faster cognitive decline on the latent PACC, independent of and synergistic with amyloid-PET burden

Study Design

Cohort Study

Sample Size

2,684 subjects

Study Duration

Median 5.4 years; maximum 13.5 years

Methodology

Longitudinal cohort study using harmonized data from six observational and clinical-trial cohorts in North America, Japan and Australia; earliest enrollment 2004, most recent follow-up 2025. Primary outcome: time to progression to cognitive impairment (MCI, dementia, or two consecutive global CDR >= 0.5).

Limitations

Selected research and trial cohorts rather than unselected primary-care populations, so absolute risk estimates will not transfer directly to general practice. Longer-horizon (10-year) estimates were constrained by data sparsity. Observational design: p-tau217 is prognostic, not a demonstrated treatment target.