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European journal of nuclear medicine and molecular imaging
Published

Tau profiling across Alzheimer's disease staging reveals vulnerability to disease pathophysiology

Authors

Gleb Bezgin, Tharick A Pascoal, Joseph Therriault, Firoza Z Lussier, Stijn Servaes, Min Su Kang, Mélissa Savard, Cécile Tissot, Jenna Stevenson, Yi-Ting Wang, Julie Ottoy, Nesrine Rahmouni, Jaime Fernandez-Arias, Seyyed Ali Hosseini, Étienne Aumont, Brandon Hall, Nina Margherita Poltronetti, Vanessa Pallen, Andréa Lessa Benedet, Nicholas J Ashton, Kaj Blennow, Henrik Zetterberg, Thomas K Karikari, Tatsuhiro Terada, Mira Chamoun, Sulantha Mathotaarachchi, Arthur Cassa Macedo, Alyssa Stevenson, Peter Kunach, Gassan Massarweh, Paolo Vitali, Jean-Paul Soucy, Yasser Iturria-Medina, Serge Gauthier, Pedro Rosa-Neto

Abstract

Eur J Nucl Med Mol Imaging. 2025 Apr 25. doi: 10.1007/s00259-025-07257-4. Online ahead of print.

ABSTRACT

BACKGROUND: Inter-individual variability in tau topography challenges the propagation hypothesis of tau aggregates.

METHODS: To address this gap, we propose the Manifold Component Analysis (MCA), for identifying pseudo-continuous profiles informed by the spatial continuity of stage regions.

RESULTS: Longitudinal and cross-sectional MCA in large aging cohort identified individual profiles (N = 753) expressing tau load in the entorhinal, limbic and neocortical regions. Using these profiles, we found neuropsychological and blood-based milestones of early and late disease stages. Finally, we also found evidence of rapid tau load increases and cognitive decline centered at the early-to-mid neocortical stages of Alzheimer's disease.

CONCLUSIONS: Stage system based on tau load and spreading profiles across cortical areas provide a compelling framework for inferring pathophysiological prognosis in Alzheimer's disease.

PMID:40274672 | DOI:10.1007/s00259-025-07257-4

UK DRI Authors

Profile picture of Henrik Zetterberg

Prof Henrik Zetterberg

Group Leader

Pioneering the development of fluid biomarkers for dementia

Prof Henrik Zetterberg