A pooled analysis of 8,582 adults from seven prospective cohorts found that higher plasma p-tau217 concentrations were associated with greater cognitive impairment risk and earlier progression, with stronger associations among APOE-ε4 carriers. Each 1-SD increase in p-tau217 was associated with a 24% shorter time to cognitive impairment among carriers compared with 13% among non-carriers, suggesting that genetic background can refine the prognostic meaning of this Alzheimer’s disease blood biomarker.