Baseline plasma %p-tau217 (ratio of phosphorylated to non-phosphorylated tau217, measured by LC-MS/MS) was evaluated as a prognostic biomarker in 982 cognitively unimpaired (CU) community-dwelling adults (age 69–85, 65% female) followed annually for up to 12 years, with replication in the same cohort using immunoassays and in an independent primary care cohort (AgeCoDe, n=1204, age >80).
Participants with Elevated or High %p-tau217 had markedly increased risks of MCI (HR 6.0–12.6) and dementia (HR 9.9–21.3) vs. the Low group; the Low group had a 92.2% 10-year negative predictive value (NPV) for any clinical progression and 98.1% NPV for dementia. The High group had a 71.6% positive predictive value (PPV) for MCI/dementia at 10 years. Immunoassays (Fujirebio, ALZPath) showed comparable NPVs but lower PPVs and weaker high-risk stratification than mass spectrometry–based %p-tau217.
- No amyloid or tau PET/CSF confirmation of pathological status, limiting ground-truth verification. - High dropout rates (reasons undetermined; may bias progression estimates toward survival) and up to 2-year follow-up gaps due to COVID-19. - Demographically narrow cohorts (predominantly Spanish and German, older adults), limiting generalizability to younger or more diverse populations.
A low plasma %p-tau217 result can reassure most CU older adults of minimal dementia risk over 10 years (NPV >92%), making it a practical front-line screening tool. Immunoassay platforms offer similar reassurance for ruling out risk, but mass spectrometry–based %p-tau217 better identifies the highest-risk individuals for clinical trial enrichment or confirmatory workup.
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