Defining patient-centered amyloid PET thresholds for the onset of tauopathy in Alzheimer's disease
(2026) In Alzheimer's and Dementia 22(1).- Abstract
INTRODUCTION: 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. METHODS: 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. RESULTS: 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... (More)
INTRODUCTION: 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. METHODS: 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. RESULTS: 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). DISCUSSION: 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. Highlights: 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.
(Less)
- author
- author collaboration
- organization
- publishing date
- 2026-01
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- amyloid positron emission tomography, amyloid positron emission tomography thresholds, tau positron emission tomography, tauopathy
- in
- Alzheimer's and Dementia
- volume
- 22
- issue
- 1
- article number
- e71064
- publisher
- Wiley
- external identifiers
-
- scopus:105026639349
- pmid:41485137
- ISSN
- 1552-5260
- DOI
- 10.1002/alz.71064
- language
- English
- LU publication?
- yes
- additional info
- Publisher Copyright: © 2026 The Author(s). Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.
- id
- 51ad6c77-fca1-47bd-a03a-054e2e136f48
- date added to LUP
- 2026-03-23 09:46:29
- date last changed
- 2026-05-18 15:29:28
@article{51ad6c77-fca1-47bd-a03a-054e2e136f48,
abstract = {{<p>INTRODUCTION: 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. METHODS: 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. RESULTS: 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). DISCUSSION: 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. Highlights: 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.</p>}},
author = {{Zhu, Zeyu and Steward, Anna and Dehsarvi, Amir and Roemer-Cassiano, Sebastian N. and Dewenter, Anna and Biel, Davina and Hirsch, Fabian and Frontzkowski, Lukas and Pescoller, Julia and Klonowski, Madleen and Gnörich, Johannes and Pontecorvo, Michael J. and Shcherbinin, Sergey and Schöll, Michael and Buckley, Rachel and Ossenkoppele, Rik and Xie, Fang and Guo, Tengfei and Höglinger, Günter and Brendel, Matthias and Franzmeier, Nicolai}},
issn = {{1552-5260}},
keywords = {{amyloid positron emission tomography; amyloid positron emission tomography thresholds; tau positron emission tomography; tauopathy}},
language = {{eng}},
number = {{1}},
publisher = {{Wiley}},
series = {{Alzheimer's and Dementia}},
title = {{Defining patient-centered amyloid PET thresholds for the onset of tauopathy in Alzheimer's disease}},
url = {{http://dx.doi.org/10.1002/alz.71064}},
doi = {{10.1002/alz.71064}},
volume = {{22}},
year = {{2026}},
}