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Cited by 308Dementia and Cognitive Impairment ResearchAlzheimer's disease research and treatmentsMedical Imaging Techniques and Applications

Biomarker modeling of Alzheimer’s disease using PET-based Braak staging

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Therriault, Joseph, Pascoal, Tharick A., Lussier, Firoza Z., Tissot, Cécile, Chamoun, Mira, Bezgin, Gleb, Servaes, Stijn, Benedet, Andrea L. +14 more·2022·Nature Aging
DOI 10.1038/s43587-022-00204-0PMC PMC10154209
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Abstract

Gold-standard diagnosis of Alzheimer’s disease (AD) relies on histopathological staging systems. Using the topographical information from [18 F]MK6240 tau positron-emission tomography (PET), we applied the Braak tau staging system to 324 living individuals. We used PET-based Braak stage to model the trajectories of amyloid-β, phosphorylated tau (pTau) in cerebrospinal fluid (pTau 181, pTau 217, pTau 231 and pTau 235) and plasma (pTau 181 and pTau 231), neurodegeneration and cognitive symptoms. We identified nonlinear AD biomarker trajectories corresponding to the spatial extent of tau-PET, with modest biomarker changes detectable by Braak stage II and significant changes occurring at stages III–IV, followed by plateaus. Early Braak stages were associated with isolated memory impairment, whereas Braak stages V–VI were incompatible with normal cognition. In 159 individuals with follow-up tau-PET, progression beyond stage III took place uniquely in the presence of amyloid-β positivity. Our findings support PET-based Braak staging as a framework to model the natural history of AD and monitor AD severity in living humans.

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References 72 · Cited by 308

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Authors
Therriault, J., Pascoal, T. A., Lussier, F. Z., Tissot, C., Chamoun, M., Bezgin, G., Servaes, S., Benedet, A. L., Ashton, N. J., Karikari, T. K., Lantero-Rodriguez, J., Kunach, P., Wang, Y.-T., Fernandez-Arias, J., Massarweh, G., Vitali, P., Soucy, J.-P., Saha-Chaudhuri, P., Blennow, K., Zetterberg, H., Gauthier, S., & Rosa-Neto, P.
Affiliations
  • Douglas Mental Health University Institute (CA)
  • University of Pittsburgh (US)
  • King's College London (GB)
  • McGill University (CA)
  • Sahlgrenska University Hospital (SE)
Corresponding author
Therriault, Joseph
ORCID
Venue
Nature Aging
Publisher
Springer Science and Business Media LLC
Published
2022-04-25
Volume
2
Issue
6
Pages
526-535
ISSN
2662-8465 (ISSN-L)
DOI
10.1038/s43587-022-00204-0
PMC
PMC10154209
OpenAlex
W4224620999
Cited by
308
References
72
Citations by year
2026: 79 · 2025: 81 · 2024: 81 · 2023: 49 · 2022: 18
FWCI
37.32
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature Aging (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • UCL Discovery (University College London) (submittedVersion)
Funders
Gouvernement du Canada | Canadian Institutes of Health Research (#170846)
Topics
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Medical Imaging Techniques and Applications
Keywords
Alzheimer's disease, Braak staging, tau PET, [18F]MK-6240, phosphorylated tau, amyloid-beta, cerebrospinal fluid biomarkers, plasma tau, neurodegeneration, cognitive decline, memory impairment, disease progression, natural history (disease), biomarker trajectories
MeSH terms
Alzheimer Disease, Humans, Biomarkers, Amyloid beta-Peptides, Positron-Emission Tomography

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