Astrocyte reactivity influences amyloid-β effects on tau pathology in preclinical Alzheimer's disease.

Humans Alzheimer Disease / pathology Amyloid beta-Peptides Astrocytes / pathology Biomarkers Cognitive Dysfunction Cross-Sectional Studies Positron-Emission Tomography tau Proteins

Journal

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

Informations de publication

Date de publication:
07 2023
Historique:
received: 23 01 2023
accepted: 01 05 2023
medline: 21 7 2023
pubmed: 30 5 2023
entrez: 29 5 2023
Statut: ppublish

Résumé

An unresolved question for the understanding of Alzheimer's disease (AD) pathophysiology is why a significant percentage of amyloid-β (Aβ)-positive cognitively unimpaired (CU) individuals do not develop detectable downstream tau pathology and, consequently, clinical deterioration. In vitro evidence suggests that reactive astrocytes unleash Aβ effects in pathological tau phosphorylation. Here, in a biomarker study across three cohorts (n = 1,016), we tested whether astrocyte reactivity modulates the association of Aβ with tau phosphorylation in CU individuals. We found that Aβ was associated with increased plasma phosphorylated tau only in individuals positive for astrocyte reactivity (Ast

Identifiants

DOI: 10.1038/s41591-023-02380-x PMID: 37248300 PMC: PMC10353939
pubmed: 37248300
doi: 10.1038/s41591-023-02380-x
pii: 10.1038/s41591-023-02380-x
pmc: PMC10353939
doi:

Substances chimiques

Amyloid beta-Peptides 0
Biomarkers 0
tau Proteins 0
APP protein, human 0
MAPT protein, human 0

Types de publication

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

Langues

eng

Sous-ensembles de citation

IM

Pagination

1775-1781

Subventions

Organisme : NIA NIH HHS
ID : R01 AG075336
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG052521
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG052528
Pays : United States
Organisme : NIA NIH HHS
ID : R37 AG023651
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG053504
Pays : United States
Organisme : NIA NIH HHS
ID : P30 AG066468
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG073267
Pays : United States
Organisme : NIA NIH HHS
ID : RF1 AG052525
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL105647
Pays : United States
Organisme : NIA NIH HHS
ID : P01 AG014449
Pays : United States
Organisme : NIA NIH HHS
ID : RF1 AG025516
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG052446
Pays : United States
Organisme : NIA NIH HHS
ID : RF1 AG053504
Pays : United States
Organisme : NHLBI NIH HHS
ID : K24 HL123565
Pays : United States
Organisme : NIA NIH HHS
ID : P01 AG025204
Pays : United States

Commentaires et corrections

Type : UpdateOf

Informations de copyright

© 2023. The Author(s).

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Auteurs

Bruna Bellaver (B)

Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA.
Graduate Program in Biological Sciences-Biochemistry, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
ORCID: 0000-0002-2212-3373

Guilherme Povala (G)

Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA.
ORCID: 0000-0002-2023-6569

Pamela C L Ferreira (PCL)

Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA.
ORCID: 0000-0003-2134-9829

João Pedro Ferrari-Souza (JP)

Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA.
Graduate Program in Biological Sciences-Biochemistry, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.

Douglas T Leffa (DT)

Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA.

Firoza Z Lussier (FZ)

Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA.

Andréa L Benedet (AL)

Department of Psychiatry and Neurochemistry, The Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.

Nicholas J Ashton (NJ)

Department of Psychiatry and Neurochemistry, The Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.
Centre for Age-Related Medicine, Stavanger University Hospital, Stavanger, Norway.
Department of Old Age Psychiatry, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.

Gallen Triana-Baltzer (G)

Neuroscience Biomarkers, Janssen Research and Development, La Jolla, CA, USA.

Hartmuth C Kolb (HC)

Neuroscience Biomarkers, Janssen Research and Development, La Jolla, CA, USA.

Cécile Tissot (C)

Translational Neuroimaging Laboratory, McGill University Research Centre for Studies in Aging, Alzheimer's Disease Research Unit, Douglas Research Institute, Le Centre intégré universitaire de santé et de services sociaux (CIUSSS) de l'Ouest-de-l'Île-de-Montréal; Department of Neurology and Neurosurgery, Psychiatry and Pharmacology and Therapeutics, McGill University, Montreal, Quebec, Canada.
ORCID: 0000-0003-2711-3833

Joseph Therriault (J)

Translational Neuroimaging Laboratory, McGill University Research Centre for Studies in Aging, Alzheimer's Disease Research Unit, Douglas Research Institute, Le Centre intégré universitaire de santé et de services sociaux (CIUSSS) de l'Ouest-de-l'Île-de-Montréal; Department of Neurology and Neurosurgery, Psychiatry and Pharmacology and Therapeutics, McGill University, Montreal, Quebec, Canada.
ORCID: 0000-0002-7826-4781

Stijn Servaes (S)

Translational Neuroimaging Laboratory, McGill University Research Centre for Studies in Aging, Alzheimer's Disease Research Unit, Douglas Research Institute, Le Centre intégré universitaire de santé et de services sociaux (CIUSSS) de l'Ouest-de-l'Île-de-Montréal; Department of Neurology and Neurosurgery, Psychiatry and Pharmacology and Therapeutics, McGill University, Montreal, Quebec, Canada.

Jenna Stevenson (J)

Translational Neuroimaging Laboratory, McGill University Research Centre for Studies in Aging, Alzheimer's Disease Research Unit, Douglas Research Institute, Le Centre intégré universitaire de santé et de services sociaux (CIUSSS) de l'Ouest-de-l'Île-de-Montréal; Department of Neurology and Neurosurgery, Psychiatry and Pharmacology and Therapeutics, McGill University, Montreal, Quebec, Canada.

Nesrine Rahmouni (N)

Translational Neuroimaging Laboratory, McGill University Research Centre for Studies in Aging, Alzheimer's Disease Research Unit, Douglas Research Institute, Le Centre intégré universitaire de santé et de services sociaux (CIUSSS) de l'Ouest-de-l'Île-de-Montréal; Department of Neurology and Neurosurgery, Psychiatry and Pharmacology and Therapeutics, McGill University, Montreal, Quebec, Canada.

Oscar L Lopez (OL)

Department of Neurology, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
ORCID: 0000-0002-8546-8256

Dana L Tudorascu (DL)

Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA.
Department of Biostatistics, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.

Victor L Villemagne (VL)

Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA.

Milos D Ikonomovic (MD)

Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA.
Department of Neurology, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
Geriatric Research Education and Clinical Center, VA Pittsburgh HS, Pittsburgh, PA, USA.

Serge Gauthier (S)

Translational Neuroimaging Laboratory, McGill University Research Centre for Studies in Aging, Alzheimer's Disease Research Unit, Douglas Research Institute, Le Centre intégré universitaire de santé et de services sociaux (CIUSSS) de l'Ouest-de-l'Île-de-Montréal; Department of Neurology and Neurosurgery, Psychiatry and Pharmacology and Therapeutics, McGill University, Montreal, Quebec, Canada.

Eduardo R Zimmer (ER)

Graduate Program in Biological Sciences-Biochemistry, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
Department of Pharmacology, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
Graduate Program in Biological Sciences: Pharmacology and Therapeutics, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
Brain Institute, PUCRS, Porto Alegre, Brazil.

Henrik Zetterberg (H)

Department of Psychiatry and Neurochemistry, The Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.
Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden.
Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, London, UK.
UK Dementia Research Institute at UCL, London, UK.
Hong Kong Center for Neurodegenerative Diseases, Hong Kong, China.
Wisconsin Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, USA.
ORCID: 0000-0003-3930-4354

Kaj Blennow (K)

Department of Psychiatry and Neurochemistry, The Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.
Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden.
ORCID: 0000-0002-1890-4193

Howard J Aizenstein (HJ)

Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA.
Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA, USA.

William E Klunk (WE)

Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA.

Beth E Snitz (BE)

Department of Neurology, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.

Pauline Maki (P)

Department of Psychiatry, University of Illinois, Chicago, IL, USA.

Rebecca C Thurston (RC)

Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA.
Department of Psychology, University of Pittsburgh, Pittsburgh, PA, USA.
Department of Epidemiology, University of Pittsburgh School of Public Health, Pittsburgh, PA, USA.
ORCID: 0000-0001-6580-1202

Ann D Cohen (AD)

Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA.

Mary Ganguli (M)

Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA.
Department of Neurology, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
Department of Epidemiology, University of Pittsburgh School of Public Health, Pittsburgh, PA, USA.

Thomas K Karikari (TK)

Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA.
Department of Psychiatry and Neurochemistry, The Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.

Pedro Rosa-Neto (P)

Translational Neuroimaging Laboratory, McGill University Research Centre for Studies in Aging, Alzheimer's Disease Research Unit, Douglas Research Institute, Le Centre intégré universitaire de santé et de services sociaux (CIUSSS) de l'Ouest-de-l'Île-de-Montréal; Department of Neurology and Neurosurgery, Psychiatry and Pharmacology and Therapeutics, McGill University, Montreal, Quebec, Canada.
Brain Imaging Centre, Montreal Neurological Institute-Hospital, Montreal, Quebec, Canada.
ORCID: 0000-0001-9116-1376

Tharick A Pascoal (TA)

Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA. pascoalt@upmc.edu.
Department of Neurology, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA. pascoalt@upmc.edu.
ORCID: 0000-0001-9057-8014

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Astrocyte reactivity influences amyloid-β...
questionsmedicales.fr › Troubles mentaux › Troubles neurocognitifs › Démence › Maladie d'Alzheimer › Astrocyte reactivity influences amyloid-β...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines membranaires › Peptides bêta-amyloïdes › Astrocyte reactivity influences amyloid-β...
questionsmedicales.fr › Cellules › Névroglie › Astrocytes › Astrocyte reactivity influences amyloid-β...
questionsmedicales.fr › Facteurs biologiques › Marqueurs biologiques › Astrocyte reactivity influences amyloid-β...
questionsmedicales.fr › Troubles mentaux › Troubles neurocognitifs › Troubles de la cognition › Dysfonctionnement cognitif › Astrocyte reactivity influences amyloid-β...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Caractéristiques des études épidémiologiques › Études épidémiologiques › Études transversales › Astrocyte reactivity influences amyloid-β...
questionsmedicales.fr › Diagnostic › Techniques et procédures diagnostiques › Techniques de diagnostic radioisotopique › Scintigraphie › Tomoscintigraphie › Tomographie par émission de positons › Astrocyte reactivity influences amyloid-β...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines de tissu nerveux › Protéines associées aux microtubules › Protéines tau › Astrocyte reactivity influences amyloid-β...