Plasma p-tau217 identifies cognitively normal older adults who will develop cognitive impairment in a 10-year window

INTRODUCTION: We assessed the prognostic accuracy of plasma p-tau217 in predicting the progression to mild cognitive impairment (MCI) in cognitively unimpaired (CU) individuals over a mean follow-up of 5.65 years after plasma collection (range 1.01-10.47). METHODS: We included 215 participants from the PREVENT-AD cohort with plasma Aβ42/40 and p-tau217, 159 with cerebrospinal fluid (CSF) Aβ42/40 and p-tau217, and 155 with ¹⁸F-NAV4694 and ¹⁸F-flortaucipir PET scans. MCI progression was determined by multidisciplinary consensus among memory experts blind to biomarker and genetic information. RESULTS: Cox proportional hazard models indicated a greater progression rate in A+T+plasma and A-T+plasma compared to A-T-plasma individuals (HR = 7.81 [95% CI = 3.92 to 15.59] and HR = 4.25 [1.60-11.31] respectively). Similar results were found with CSF (HR = 3.63 [1.72-7.70]) and PET (HR = 9.30 [3.67-23.55]). DISCUSSION: Plasma p-tau217 is a prognostic marker for identifying individuals who will develop cognitive impairment within ten years. HIGHLIGHTS: Elevated plasma p-tau217 levels in CU individuals indicate future clinical progression. Adding plasma Aβ42/40 status to p-tau markers did not improve the prediction to MCI. All individuals with abnormal tau PET measured in a temporal meta-ROI progressed to MCI.