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

Does plasma phosphorylated tau 217 (p-tau217) predict absolute long-term risk of clinical progression in cognitively unimpaired older adults across multiple aging and Alzheimer disease cohorts?In this pooled multicohort study of 2684 cognitively unimpaired participants across 6 selected longitudinal studies, higher baseline plasma p-tau217 levels were significantly associated with increased risk of progression to cognitive impairment over up to 13.5 years of follow-up. Individuals with very high p-tau217 levels (>2.5 SD) had an estimated 38% absolute risk of progression over 5 years, with higher risk over 10 years, although longer-horizon estimates were constrained by sparsity of data.These findings support the potential of p-tau217 for prognostic model development and estimation of long-term risk of cognitive decline among cognitively unimpaired individuals, although further research in unselected and more generalizable populations is needed.

Corresponding Author: Reisa A. Sperling, MD, Department of Neurology, Mass General Brigham, 60 Fenwood Rd, Boston, MA 02115 (reisa@bwh.harvard.edu).

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