TY  - JOUR
AU  - Zhu, Zeyu
AU  - Steward, Anna
AU  - Dehsarvi, Amir
AU  - Roemer-Cassiano, Sebastian N.
AU  - Dewenter, Anna
AU  - Biel, Davina
AU  - Hirsch, Fabian
AU  - Frontzkowski, Lukas
AU  - Pescoller, Julia
AU  - Klonowski, Madleen
AU  - Gnoerich, Johannes
AU  - Pontecorvo, Michael J.
AU  - Shcherbinin, Sergey
AU  - Schöll, Michael
AU  - Buckley, Rachel
AU  - Ossenkoppele, Rik
AU  - Xie, Fang
AU  - Guo, Tengfei
AU  - Höglinger, Günter
AU  - Brendel, Matthias
AU  - Franzmeier, Nicolai
TI  - Defining patient‐centered amyloid PET thresholds for the onset of tauopathy in Alzheimer's disease
JO  - Alzheimer's and dementia
VL  - 22
IS  - 1
SN  - 1552-5260
CY  - Hoboken, NJ
PB  - Wiley
M1  - DZNE-2026-00018
SP  - e71064
PY  - 2026
AB  - 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.
KW  - Humans
KW  - Positron-Emission Tomography
KW  - Male
KW  - Alzheimer Disease: diagnostic imaging
KW  - Alzheimer Disease: metabolism
KW  - Female
KW  - Tauopathies: diagnostic imaging
KW  - Tauopathies: metabolism
KW  - Aged
KW  - tau Proteins: metabolism
KW  - Aged, 80 and over
KW  - Amyloid: metabolism
KW  - Sex Factors
KW  - Age Factors
KW  - Brain: diagnostic imaging
KW  - Brain: metabolism
KW  - Carbolines
LB  - PUB:(DE-HGF)16
C6  - pmid:41485137
DO  - DOI:10.1002/alz.71064
UR  - https://pub.dzne.de/record/283122
ER  -