Plasma p‐tau217 identifies cognitively normal older adults who will develop cognitive impairment in a 10‐year window
Yara Yakoub, Fernando González‐Ortiz, Nicholas J. Ashton, Christine Déry, Cherie Strikwerda‐Brown, Frédéric St‐Onge, Valentin Ourry, Michael Schöll, Maiya R. Geddes, Simon Ducharme, Maxime Montembeault, Pedro Rosa‐Neto, Jean‐Paul Soucy, John C.S. Breitner, Henrik Zetterberg, Kaj Blennow, Judes Poirier, Sylvia Villeneuve
Abstract
Abstract 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 Aβ 42/40 and p‐tau217, 159 with cerebrospinal fluid (CSF) Aβ 42/40 and p‐tau217, and 155 with 18 F‐NAV4694 and 18 F‐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 Aβ 42/40 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.