Defining patient‐centered amyloid PET thresholds for the onset of tauopathy in Alzheimer's disease

Zhu, Zeyu; Steward, Anna; Dehsarvi, Amir; Roemer‐Cassiano, Sebastian N.; Dewenter, Anna; Biel, Davina; Hirsch, Fabian; Frontzkowski, Lukas; Pescoller, Julia; Klonowski, Madleen; Gnörich, Johannes; Pontecorvo, Michael J.; Shcherbinin, Sergey; Schöll, Michael; Buckley, Rachel; Ossenkoppele, Rik; Xie, Fang; Guo, Tengfei; Höglinger, Günter U. ; Brendel, Matthias und Franzmeier, Nicolai (2026): Defining patient‐centered amyloid PET thresholds for the onset of tauopathy in Alzheimer's disease. In: Alzheimer's & Dementia, Bd. 22, Nr. 1, e71064

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 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.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Medizin > Munich Cluster for Systems Neurology (SyNergy) ; Medizin > Institut für Schlaganfall- und Demenzforschung (ISD)
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• ISSN: 1552-5260
• Sprache: Englisch