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Plasma p-tau217 and tau-PET predict future cognitive decline among cognitively unimpaired individuals: implications for clinical trials

Title: Plasma p-tau217 and tau-PET predict future cognitive decline among cognitively unimpaired individuals: implications for clinical trials
Authors: Ossenkoppele, R; Salvadó, G; Janelidze, S; Pichet Binette, A; Bali, D; Karlsson, L; Palmqvist, S; Mattsson-Carlgren, N; Stomrud, E; Therriault, J; Rahmouni, N; Rosa-Neto, P; Coomans, EM; van de Giessen, E; van der Flier, WM; Teunissen, CE; Jonaitis, EM; Johnson, SC; Villeneuve, S; Benzinger, TLS; Schindler, SE; Bateman, RJ; Doecke, JD; Doré, V; Feizpour, A; Masters, CL; Rowe, C; Wiste, HJ; Petersen, RC; Jack, CR; Hansson, O
Publisher Information: Springer Science and Business Media LLC
Publication Year: 2025
Collection: The University of Melbourne: Digital Repository
Description: Plasma p-tau217 and tau positron emission tomography (PET) are strong prognostic biomarkers in Alzheimer's disease (AD), but their relative performance in predicting future cognitive decline among cognitively unimpaired (CU) individuals is unclear. In a head-to-head comparison study including nine cohorts and 1,474 individuals, we show that plasma p-tau217 and medial temporal lobe tau-PET signal display similar associations with cognitive decline on a global cognitive composite test (R2PET = 0.34 versus R2plasma = 0.33, Pdifference = 0.653) and with progression to mild cognitive impairment (hazard ratio (HR)PET = 1.61 (1.48-1.76) versus HRplasma = 1.57 (1.43-1.72), Pdifference = 0.322). Combined plasma and PET models were superior to the single-biomarker models (R2 = 0.35, P < 0.01). Sequential selection using plasma phosphorylated tau at threonine 217 (p-tau217) and then tau-PET reduced the number of participants required for a clinical trial by 94%, compared to a 76% reduction when using plasma p-tau217 alone. Thus, plasma p-tau217 and tau-PET showed similar performance for predicting future cognitive decline in CU individuals, and their sequential use enhances screening efficiency for preclinical AD trials.
Document Type: article in journal/newspaper
Language: English
ISSN: 2662-8465
Relation: NHMRC/1152623; https://hdl.handle.net/11343/360325
Availability: https://hdl.handle.net/11343/360325
Rights: https://creativecommons.org/licenses/by/4.0 ; CC BY
Accession Number: edsbas.6A660918
Database: BASE