biostudies-literatureUnknownXu Y<h4>Background</h4><i>APOE</i> -ρ.4 is the strongest genetic risk factor for Alzheimer's disease (AD), and plasma phosphorylated tau217 (P-tau217) is a highly sensitive and specific biomarker for AD pathology. Their combined utility to predict cognitive decline before onset of AD has not been systematically evaluated.<h4>Methods</h4>Using longitudinal data from multiple cohorts, we evaluated plasma P-tau217 as a predictor of when cognitive impairment occurs in AD. P-tau217 concentrations were analyzed as continuous and binary variables using cohort-specific biomarker positivity thresholds. Association of plasma P-tau217 with prevalent and incident cognitive impairment were assessed using logistic regression and Cox models, stratified by <i>APOE</i> genotype. Adjusted survival curves and remedRxiv : the preprint server for health sciences2026.02.06.26345774https://www.ebi.ac.uk/biostudies/studies/S-EPMC12919147biostudies-literaturePredictive Value of Plasma P-tau217 and &lt;i&gt;APOE&lt;/i&gt; Genotype for Preclinical Cognitive Decline in Alzheimer's Disease.PMC12919147Petersen MMejia DRReyes RERWilson RMayeux RGu YO'Bryant SMedrano MBrickman AMReyes-Dumeyer DJohnson SManly JJEngelman CDGunasekaran TIBennett DASanchez DHonig LPiriz ALantigua RAAsthana SXu YVardarajan BNfalsePredictive Value of Plasma P-tau217 and &lt;i&gt;APOE&lt;/i&gt; Genotype for Preclinical Cognitive Decline in Alzheimer's Disease.<h4>Background</h4><i>APOE</i> -ρ.4 is the strongest genetic risk factor for Alzheimer's disease (AD), and plasma phosphorylated tau217 (P-tau217) is a highly sensitive and specific biomarker for AD pathology. Their combined utility to predict cognitive decline before onset of AD has not been systematically evaluated.<h4>Methods</h4>Using longitudinal data from multiple cohorts, we evaluated plasma P-tau217 as a predictor of when cognitive impairment occurs in AD. P-tau217 concentrations were analyzed as continuous and binary variables using cohort-specific biomarker positivity thresholds. Association of plasma P-tau217 with prevalent and incident cognitive impairment were assessed using logistic regression and Cox models, stratified by <i>APOE</i> genotype. Adjusted survival curves and re2026-01-01T00:00:00Z2026 Feb2026-07-12T03:14:53.452Z2026-07-12T03:11:15.578ZS-EPMC129191474172830110.64898/2026.02.06.26345774