Plasma P-tau217 significantly predicted longitudinal cognitive decline in both cohorts in this prognostic study of data from two preclinical AD cohort studies involving 171 cognitively unimpaired individuals with cerebrospinal fluid or positron emission tomographic measures of β-amyloid positivity. These findings imply that plasma P-tau217 could be used in clinical trials of novel disease-modifying treatments as a supplement to CSF or PET for participant selection.