Journal Article

DZNE-2026-00018

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Defining patient‐centered amyloid PET thresholds for the onset of tauopathy in Alzheimer's disease

Zhu, Z. ; Steward, A. ; Dehsarvi, A. ; Roemer-Cassiano, S. N. ; Dewenter, A. ; Biel, D. ; Hirsch, F. ; Frontzkowski, L. ; Pescoller, J. ; Klonowski, M. ; Gnoerich, J.Extern* ; Pontecorvo, M. J. ; Shcherbinin, S. ; Schöll, M. ; Buckley, R. ; Ossenkoppele, R. ; Xie, F. ; Guo, T. ; Höglinger, G.DZNE* ; Brendel, M.DZNE* ; Franzmeier, N.

2026
Wiley Hoboken, NJ

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Please use a persistent id in citations: doi:10.1002/alz.71064

Abstract: 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.

Keyword(s): Humans (MeSH) ; Positron-Emission Tomography (MeSH) ; Male (MeSH) ; Alzheimer Disease: diagnostic imaging (MeSH) ; Alzheimer Disease: metabolism (MeSH) ; Female (MeSH) ; Tauopathies: diagnostic imaging (MeSH) ; Tauopathies: metabolism (MeSH) ; Aged (MeSH) ; tau Proteins: metabolism (MeSH) ; Aged, 80 and over (MeSH) ; Amyloid: metabolism (MeSH) ; Sex Factors (MeSH) ; Age Factors (MeSH) ; Brain: diagnostic imaging (MeSH) ; Brain: metabolism (MeSH) ; Carbolines (MeSH)

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Contributing Institute(s):

1. Clinical Research (Munich) (Clinical Research (Munich))
2. Molecular Neurodegeneration (AG Haass)

Research Program(s):

1. 353 - Clinical and Health Care Research (POF4-353) (POF4-353)
2. 352 - Disease Mechanisms (POF4-352) (POF4-352)

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Database coverage:
; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; DEAL Wiley ; Essential Science Indicators ; IF >= 10 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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