Plasma phosphorylated tau 217 concentrations, APOE genotype, and timing of cognitive impairment in individuals across diverse racial and ethnic groups: a pooled analysis of prospective cohort studies.

Higher baseline plasma p-tau217 predicts cognitive impairment in a pooled multi-ethnic cohort, with APOE-ε4 carriers showing stronger risk and earlier timing per 1-SD increase.

• Why it matters: Plasma p-tau217 can rise before symptoms, but it is unclear whether APOE genotype adds prognostic value for estimating who will decline and when.
• What they did: The study pooled participant-level data from seven multi-ethnic prospective cohorts in Canada, Dominican Republic, and USA (1992–2025), using logistic regression and Cox models stratified by APOE-ε4, plus survival analyses and random survival forests.
• The result: Baseline p-tau217 was linked to prevalent impairment (OR 1·77, 95% CI 1·42–2·20) and incident impairment (HR 1·41, 95% CI 1·22–1·64 per 1-SD), with stronger effects in APOE-ε4 carriers (OR 2·25; HR 1·76) and earlier cognitive-impairment-free survival emerging 3–4 years after biomarker assessment.

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