%0 Journal Article
%A Zhu, Zeyu
%A Steward, Anna
%A Dehsarvi, Amir
%A Roemer-Cassiano, Sebastian N.
%A Dewenter, Anna
%A Biel, Davina
%A Hirsch, Fabian
%A Frontzkowski, Lukas
%A Pescoller, Julia
%A Klonowski, Madleen
%A Gnoerich, Johannes
%A Pontecorvo, Michael J.
%A Shcherbinin, Sergey
%A Schöll, Michael
%A Buckley, Rachel
%A Ossenkoppele, Rik
%A Xie, Fang
%A Guo, Tengfei
%A Höglinger, Günter
%A Brendel, Matthias
%A Franzmeier, Nicolai
%T Defining patient‐centered amyloid PET thresholds for the onset of tauopathy in Alzheimer's disease
%J Alzheimer's and dementia
%V 22
%N 1
%@ 1552-5260
%C Hoboken, NJ
%I Wiley
%M DZNE-2026-00018
%P e71064
%D 2026
%X Amyloid-induced tauopathy drives clinical decline in Alzheimer's disease (AD). Because age and sex shape tau trajectories, defining patient-centered amyloid thresholds for tauopathy onset could facilitate pre-tauopathy AD identification and aid treatment decisions and prognosis.By including two samples (Alzheimer's Disease Neuroimaging Initiative [ADNI, n = 301]; and 18F-AV-1451-A05 [A05, n = 143]), we explored whether age and sex affect tauopathy transition and determined patient-centered amyloid positron emission tomography (PET) thresholds that mark tauopathy onset.We found a consistent amyloid PET × age interaction on global tau PET increase in men (ADNI/A05: p = 0.0078/0.018), with younger men showing faster amyloid-associated tau accumulation. We then established patient-centered, amyloid PET-inferred tauopathy transition cut-offs. Women reached this transition at lower amyloid PET levels, and these cutoffs predicted both earlier onset and accelerated cognitive decline (p < 0.001).This study highlights the effect of age and sex on the amyloid-to-tauopathy transition, establishes patient-centered amyloid PET thresholds for tauopathy onset, and links these thresholds to accelerated cognitive decline.Younger age is related to faster amyloid-related tau accumulation in men. We defined a series of amyloid positron emission tomography (PET) thresholds to enable patient-centered inference of amyloid-related tauopathy. Crossing the amyloid PET-defined tauopathy phase is associated with more progressive tau deposition and cognitive decline.
%K Humans
%K Positron-Emission Tomography
%K Male
%K Alzheimer Disease: diagnostic imaging
%K Alzheimer Disease: metabolism
%K Female
%K Tauopathies: diagnostic imaging
%K Tauopathies: metabolism
%K Aged
%K tau Proteins: metabolism
%K Aged, 80 and over
%K Amyloid: metabolism
%K Sex Factors
%K Age Factors
%K Brain: diagnostic imaging
%K Brain: metabolism
%K Carbolines
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:41485137
%R 10.1002/alz.71064
%U https://pub.dzne.de/record/283122