Differential roles of Aβ42/40, p-tau231 and p-tau217 for Alzheimer's trial selection and disease monitoring.

Humans Alzheimer Disease / pathology tau Proteins Amyloid beta-Peptides Cognitive Dysfunction Disease Progression Biomarkers Atrophy

Journal

Nature medicine
ISSN: 1546-170X
Titre abrégé: Nat Med
Pays: United States
ID NLM: 9502015

Informations de publication

Date de publication:
12 2022
Historique:
received: 24 04 2022
accepted: 03 10 2022
pubmed: 2 12 2022
medline: 3 1 2023
entrez: 1 12 2022
Statut: ppublish

Résumé

Blood biomarkers indicative of Alzheimer's disease (AD) pathology are altered in both preclinical and symptomatic stages of the disease. Distinctive biomarkers may be optimal for the identification of AD pathology or monitoring of disease progression. Blood biomarkers that correlate with changes in cognition and atrophy during the course of the disease could be used in clinical trials to identify successful interventions and thereby accelerate the development of efficient therapies. When disease-modifying treatments become approved for use, efficient blood-based biomarkers might also inform on treatment implementation and management in clinical practice. In the BioFINDER-1 cohort, plasma phosphorylated (p)-tau231 and amyloid-β42/40 ratio were more changed at lower thresholds of amyloid pathology. Longitudinally, however, only p-tau217 demonstrated marked amyloid-dependent changes over 4-6 years in both preclinical and symptomatic stages of the disease, with no such changes observed in p-tau231, p-tau181, amyloid-β42/40, glial acidic fibrillary protein or neurofilament light. Only longitudinal increases of p-tau217 were also associated with clinical deterioration and brain atrophy in preclinical AD. The selective longitudinal increase of p-tau217 and its associations with cognitive decline and atrophy was confirmed in an independent cohort (Wisconsin Registry for Alzheimer's Prevention). These findings support the differential association of plasma biomarkers with disease development and strongly highlight p-tau217 as a surrogate marker of disease progression in preclinical and prodromal AD, with impact for the development of new disease-modifying treatments.

Identifiants

DOI: 10.1038/s41591-022-02074-w PMID: 36456833 PMC: PMC9800279
pubmed: 36456833
doi: 10.1038/s41591-022-02074-w
pii: 10.1038/s41591-022-02074-w
pmc: PMC9800279
doi:

Substances chimiques

amyloid beta-protein (1-42) 0
tau Proteins 0
Amyloid beta-Peptides 0
Biomarkers 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't Research Support, N.I.H., Extramural

Langues

eng

Sous-ensembles de citation

IM

Pagination

2555-2562

Subventions

Organisme : NIA NIH HHS
ID : P30 AG062715
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG068398
Pays : United States

Informations de copyright

© 2022. The Author(s).

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Auteurs

Nicholas J Ashton (NJ)

Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.
King's College London, Institute of Psychiatry, Psychology and Neuroscience, Maurice Wohl Institute Clinical Neuroscience Institute, London, UK.
NIHR Biomedical Research Centre for Mental Health and Biomedical Research Unit for Dementia at South London and Maudsley NHS Foundation, London, UK.
Centre for Age-Related Medicine, Stavanger University Hospital, Stavanger, Norway.

Shorena Janelidze (S)

Clinical Memory Research Unit, Faculty of Medicine, Lund University, Lund, Sweden.
ORCID: 0000-0003-2869-8378

Niklas Mattsson-Carlgren (N)

Clinical Memory Research Unit, Faculty of Medicine, Lund University, Lund, Sweden.
Department of Neurology, Skåne University Hospital, Lund University, Lund, Sweden.
Wallenberg Center for Molecular Medicine, Lund University, Lund, Sweden.

Alexa Pichet Binette (AP)

Clinical Memory Research Unit, Faculty of Medicine, Lund University, Lund, Sweden.
ORCID: 0000-0001-5218-3337

Olof Strandberg (O)

Clinical Memory Research Unit, Faculty of Medicine, Lund University, Lund, Sweden.

Wagner S Brum (WS)

Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.
Graduate Program in Biological Sciences: Biochemistry, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Brazil.

Thomas K Karikari (TK)

Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.
Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA.
ORCID: 0000-0003-1422-4358

Fernándo González-Ortiz (F)

Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.

Guglielmo Di Molfetta (G)

Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.

Francisco J Meda (FJ)

Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.
ORCID: 0000-0002-3343-7351

Erin M Jonaitis (EM)

Wisconsin Alzheimer's Institute, School of Medicine and Public Health, University of Wisconsin, Madison, WI, USA.
Wisconsin Alzheimer's Disease Research Center, School of Medicine and Public Health, University of Wisconsin, Madison, WI, USA.

Rebecca Langhough Koscik (RL)

Wisconsin Alzheimer's Institute, School of Medicine and Public Health, University of Wisconsin, Madison, WI, USA.
Wisconsin Alzheimer's Disease Research Center, School of Medicine and Public Health, University of Wisconsin, Madison, WI, USA.
ORCID: 0000-0003-0025-744X

Karly Cody (K)

Wisconsin Alzheimer's Institute, School of Medicine and Public Health, University of Wisconsin, Madison, WI, USA.
Wisconsin Alzheimer's Disease Research Center, School of Medicine and Public Health, University of Wisconsin, Madison, WI, USA.
ORCID: 0000-0001-5996-2560

Tobey J Betthauser (TJ)

Wisconsin Alzheimer's Institute, School of Medicine and Public Health, University of Wisconsin, Madison, WI, USA.
Wisconsin Alzheimer's Disease Research Center, School of Medicine and Public Health, University of Wisconsin, Madison, WI, USA.
ORCID: 0000-0001-8856-1352

Yan Li (Y)

Department of Neurology, Washington University School of Medicine, St. Louis, MO, USA.
SILQ Center, Washington University School of Medicine, St. Louis, MO, USA.

Eugeen Vanmechelen (E)

ADx NeuroSciences, Technologiepark 94, Ghent, Belgium.
ORCID: 0000-0002-9466-5366

Sebastian Palmqvist (S)

Clinical Memory Research Unit, Faculty of Medicine, Lund University, Lund, Sweden.
Memory Clinic, Skåne University Hospital, Malmö, Sweden.
ORCID: 0000-0002-9267-1930

Erik Stomrud (E)

Clinical Memory Research Unit, Faculty of Medicine, Lund University, Lund, Sweden.
Memory Clinic, Skåne University Hospital, Malmö, Sweden.

Randall J Bateman (RJ)

Department of Neurology, Washington University School of Medicine, St. Louis, MO, USA.
SILQ Center, Washington University School of Medicine, St. Louis, MO, USA.
ORCID: 0000-0002-7729-1702

Henrik Zetterberg (H)

Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.
Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden.
Department of Neurodegenerative Disease, UCL Institute of Neurology, Queen Square, London, UK.
UK Dementia Research Institute at UCL, London, UK.
Hong Kong Center for Neurodegenerative Diseases, Hong Kong, China.
ORCID: 0000-0003-3930-4354

Sterling C Johnson (SC)

Wisconsin Alzheimer's Institute, School of Medicine and Public Health, University of Wisconsin, Madison, WI, USA.
Wisconsin Alzheimer's Disease Research Center, School of Medicine and Public Health, University of Wisconsin, Madison, WI, USA.
ORCID: 0000-0002-8501-545X

Kaj Blennow (K)

Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden. kaj.blennow@neuro.gu.se.
ADx NeuroSciences, Technologiepark 94, Ghent, Belgium. kaj.blennow@neuro.gu.se.
ORCID: 0000-0002-1890-4193

Oskar Hansson (O)

Clinical Memory Research Unit, Faculty of Medicine, Lund University, Lund, Sweden. oskar.hansson@med.lu.se.
Memory Clinic, Skåne University Hospital, Malmö, Sweden. oskar.hansson@med.lu.se.
ORCID: 0000-0001-8467-7286

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Differential roles of Aβ42/40, p-tau231 and...
questionsmedicales.fr › Troubles mentaux › Troubles neurocognitifs › Démence › Maladie d'Alzheimer › Differential roles of Aβ42/40, p-tau231 and...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines de tissu nerveux › Protéines associées aux microtubules › Protéines tau › Differential roles of Aβ42/40, p-tau231 and...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines membranaires › Peptides bêta-amyloïdes › Differential roles of Aβ42/40, p-tau231 and...
questionsmedicales.fr › Troubles mentaux › Troubles neurocognitifs › Troubles de la cognition › Dysfonctionnement cognitif › Differential roles of Aβ42/40, p-tau231 and...
questionsmedicales.fr › États, signes et symptômes pathologiques › Processus pathologiques › Caractéristiques de la maladie › Évolution de la maladie › Differential roles of Aβ42/40, p-tau231 and...
questionsmedicales.fr › Facteurs biologiques › Marqueurs biologiques › Differential roles of Aβ42/40, p-tau231 and...
questionsmedicales.fr › États, signes et symptômes pathologiques › États anatomopathologiques › Atrophie › Differential roles of Aβ42/40, p-tau231 and...