Cortical microstructural correlates of astrocytosis in autosomal-dominant Alzheimer disease.

Adult Alzheimer Disease / metabolism Amyloid beta-Protein Precursor / genetics Brain / pathology Carbon Radioisotopes / metabolism Cerebral Cortex / metabolism Deuterium / metabolism Female Heterozygote Humans Magnetic Resonance Imaging Male Middle Aged Mutation Neuroimaging Neuropsychological Tests Positron-Emission Tomography Presenilin-1 / genetics Prodromal Symptoms Selegiline / metabolism

Journal

Neurology
ISSN: 1526-632X
Titre abrégé: Neurology
Pays: United States
ID NLM: 0401060

Informations de publication

Date de publication:
12 05 2020
Historique:
received: 02 05 2019
accepted: 18 11 2019
pubmed: 16 4 2020
medline: 5 9 2020
entrez: 16 4 2020
Statut: ppublish

Résumé

To study the macrostructural and microstructural MRI correlates of brain astrocytosis, measured with The total sample (n = 31) comprised ADAD mutation carriers (n = 10 presymptomatic, 39.2 ± 10.6 years old; n = 3 symptomatic, 55.5 ± 2.0 years old) and noncarriers (n = 18, 44.0 ± 13.7 years old) belonging to families with mutations in either the presenilin-1 or amyloid precursor protein genes. All participants underwent structural and diffusion MRI and neuropsychological assessment, and 20 participants (6 presymptomatic and 3 symptomatic mutation carriers and 11 noncarriers) also underwent Vertex-wise interaction analyses revealed a differential relationship between carriers and noncarriers in the association between Our proof-of-concept study is the first to show that microstructural and macrostructural changes can reflect underlying neuroinflammatory mechanisms in early stages of Alzheimer disease (AD). The findings support a role for neuroinflammation in AD pathogenesis, with potential implications for the correct interpretation of neuroimaging biomarkers as surrogate endpoints in clinical trials.

Identifiants

DOI: 10.1212/WNL.0000000000009405 PMID: 32291295 PMC: PMC7282881
pubmed: 32291295
pii: WNL.0000000000009405
doi: 10.1212/WNL.0000000000009405
pmc: PMC7282881
doi:

Substances chimiques

Amyloid beta-Protein Precursor 0
Carbon Radioisotopes 0
Presenilin-1 0
Selegiline 2K1V7GP655
Deuterium AR09D82C7G

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

e2026-e2036

Informations de copyright

Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.

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Auteurs

Eduard Vilaplana (E)

From the Memory Unit, Department of Neurology (E.V., V.M., A.L., J.F.), Hospital de la Santa Creu i Sant Pau, Biomedical Research Institute Sant Pau, Universitat Autònoma de Barcelona; Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas, CIBERNED (E.V., V.M., A.L., J.F.), Madrid, Spain; Department of Neurobiology (E.R.-V., D.F., O.A., E.W., A.N.), Care Sciences and Society, Center for Alzheimer Research, Division of Clinical Geriatrics, and Division of Neurogeriatrics (C.G.), Karolinska Institutet, Stockholm Department of Psychology (O.A.), Stockholm University; The Aging Brain Unit (O.A., A.N.) and Unit for Hereditary Dementias (C.G.), Theme Aging, Karolinska University Hospital, Stockholm; Department of Surgical Sciences, Section of Nuclear Medicine & PET (A.W.), Uppsala University, Sweden; and Department of Neuroimaging (E.W.), Centre for Neuroimaging Sciences, Institute of Psychiatry, Psychology and Neuroscience, King's College London, United Kingdom.
ORCID: 0000-0002-1809-8435

Elena Rodriguez-Vieitez (E)

From the Memory Unit, Department of Neurology (E.V., V.M., A.L., J.F.), Hospital de la Santa Creu i Sant Pau, Biomedical Research Institute Sant Pau, Universitat Autònoma de Barcelona; Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas, CIBERNED (E.V., V.M., A.L., J.F.), Madrid, Spain; Department of Neurobiology (E.R.-V., D.F., O.A., E.W., A.N.), Care Sciences and Society, Center for Alzheimer Research, Division of Clinical Geriatrics, and Division of Neurogeriatrics (C.G.), Karolinska Institutet, Stockholm Department of Psychology (O.A.), Stockholm University; The Aging Brain Unit (O.A., A.N.) and Unit for Hereditary Dementias (C.G.), Theme Aging, Karolinska University Hospital, Stockholm; Department of Surgical Sciences, Section of Nuclear Medicine & PET (A.W.), Uppsala University, Sweden; and Department of Neuroimaging (E.W.), Centre for Neuroimaging Sciences, Institute of Psychiatry, Psychology and Neuroscience, King's College London, United Kingdom.
ORCID: 0000-0002-6639-8141

Daniel Ferreira (D)

From the Memory Unit, Department of Neurology (E.V., V.M., A.L., J.F.), Hospital de la Santa Creu i Sant Pau, Biomedical Research Institute Sant Pau, Universitat Autònoma de Barcelona; Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas, CIBERNED (E.V., V.M., A.L., J.F.), Madrid, Spain; Department of Neurobiology (E.R.-V., D.F., O.A., E.W., A.N.), Care Sciences and Society, Center for Alzheimer Research, Division of Clinical Geriatrics, and Division of Neurogeriatrics (C.G.), Karolinska Institutet, Stockholm Department of Psychology (O.A.), Stockholm University; The Aging Brain Unit (O.A., A.N.) and Unit for Hereditary Dementias (C.G.), Theme Aging, Karolinska University Hospital, Stockholm; Department of Surgical Sciences, Section of Nuclear Medicine & PET (A.W.), Uppsala University, Sweden; and Department of Neuroimaging (E.W.), Centre for Neuroimaging Sciences, Institute of Psychiatry, Psychology and Neuroscience, King's College London, United Kingdom.

Victor Montal (V)

From the Memory Unit, Department of Neurology (E.V., V.M., A.L., J.F.), Hospital de la Santa Creu i Sant Pau, Biomedical Research Institute Sant Pau, Universitat Autònoma de Barcelona; Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas, CIBERNED (E.V., V.M., A.L., J.F.), Madrid, Spain; Department of Neurobiology (E.R.-V., D.F., O.A., E.W., A.N.), Care Sciences and Society, Center for Alzheimer Research, Division of Clinical Geriatrics, and Division of Neurogeriatrics (C.G.), Karolinska Institutet, Stockholm Department of Psychology (O.A.), Stockholm University; The Aging Brain Unit (O.A., A.N.) and Unit for Hereditary Dementias (C.G.), Theme Aging, Karolinska University Hospital, Stockholm; Department of Surgical Sciences, Section of Nuclear Medicine & PET (A.W.), Uppsala University, Sweden; and Department of Neuroimaging (E.W.), Centre for Neuroimaging Sciences, Institute of Psychiatry, Psychology and Neuroscience, King's College London, United Kingdom.

Ove Almkvist (O)

From the Memory Unit, Department of Neurology (E.V., V.M., A.L., J.F.), Hospital de la Santa Creu i Sant Pau, Biomedical Research Institute Sant Pau, Universitat Autònoma de Barcelona; Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas, CIBERNED (E.V., V.M., A.L., J.F.), Madrid, Spain; Department of Neurobiology (E.R.-V., D.F., O.A., E.W., A.N.), Care Sciences and Society, Center for Alzheimer Research, Division of Clinical Geriatrics, and Division of Neurogeriatrics (C.G.), Karolinska Institutet, Stockholm Department of Psychology (O.A.), Stockholm University; The Aging Brain Unit (O.A., A.N.) and Unit for Hereditary Dementias (C.G.), Theme Aging, Karolinska University Hospital, Stockholm; Department of Surgical Sciences, Section of Nuclear Medicine & PET (A.W.), Uppsala University, Sweden; and Department of Neuroimaging (E.W.), Centre for Neuroimaging Sciences, Institute of Psychiatry, Psychology and Neuroscience, King's College London, United Kingdom.

Anders Wall (A)

From the Memory Unit, Department of Neurology (E.V., V.M., A.L., J.F.), Hospital de la Santa Creu i Sant Pau, Biomedical Research Institute Sant Pau, Universitat Autònoma de Barcelona; Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas, CIBERNED (E.V., V.M., A.L., J.F.), Madrid, Spain; Department of Neurobiology (E.R.-V., D.F., O.A., E.W., A.N.), Care Sciences and Society, Center for Alzheimer Research, Division of Clinical Geriatrics, and Division of Neurogeriatrics (C.G.), Karolinska Institutet, Stockholm Department of Psychology (O.A.), Stockholm University; The Aging Brain Unit (O.A., A.N.) and Unit for Hereditary Dementias (C.G.), Theme Aging, Karolinska University Hospital, Stockholm; Department of Surgical Sciences, Section of Nuclear Medicine & PET (A.W.), Uppsala University, Sweden; and Department of Neuroimaging (E.W.), Centre for Neuroimaging Sciences, Institute of Psychiatry, Psychology and Neuroscience, King's College London, United Kingdom.

Alberto Lleó (A)

From the Memory Unit, Department of Neurology (E.V., V.M., A.L., J.F.), Hospital de la Santa Creu i Sant Pau, Biomedical Research Institute Sant Pau, Universitat Autònoma de Barcelona; Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas, CIBERNED (E.V., V.M., A.L., J.F.), Madrid, Spain; Department of Neurobiology (E.R.-V., D.F., O.A., E.W., A.N.), Care Sciences and Society, Center for Alzheimer Research, Division of Clinical Geriatrics, and Division of Neurogeriatrics (C.G.), Karolinska Institutet, Stockholm Department of Psychology (O.A.), Stockholm University; The Aging Brain Unit (O.A., A.N.) and Unit for Hereditary Dementias (C.G.), Theme Aging, Karolinska University Hospital, Stockholm; Department of Surgical Sciences, Section of Nuclear Medicine & PET (A.W.), Uppsala University, Sweden; and Department of Neuroimaging (E.W.), Centre for Neuroimaging Sciences, Institute of Psychiatry, Psychology and Neuroscience, King's College London, United Kingdom.

Eric Westman (E)

From the Memory Unit, Department of Neurology (E.V., V.M., A.L., J.F.), Hospital de la Santa Creu i Sant Pau, Biomedical Research Institute Sant Pau, Universitat Autònoma de Barcelona; Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas, CIBERNED (E.V., V.M., A.L., J.F.), Madrid, Spain; Department of Neurobiology (E.R.-V., D.F., O.A., E.W., A.N.), Care Sciences and Society, Center for Alzheimer Research, Division of Clinical Geriatrics, and Division of Neurogeriatrics (C.G.), Karolinska Institutet, Stockholm Department of Psychology (O.A.), Stockholm University; The Aging Brain Unit (O.A., A.N.) and Unit for Hereditary Dementias (C.G.), Theme Aging, Karolinska University Hospital, Stockholm; Department of Surgical Sciences, Section of Nuclear Medicine & PET (A.W.), Uppsala University, Sweden; and Department of Neuroimaging (E.W.), Centre for Neuroimaging Sciences, Institute of Psychiatry, Psychology and Neuroscience, King's College London, United Kingdom.
ORCID: 0000-0002-3115-2977

Caroline Graff (C)

From the Memory Unit, Department of Neurology (E.V., V.M., A.L., J.F.), Hospital de la Santa Creu i Sant Pau, Biomedical Research Institute Sant Pau, Universitat Autònoma de Barcelona; Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas, CIBERNED (E.V., V.M., A.L., J.F.), Madrid, Spain; Department of Neurobiology (E.R.-V., D.F., O.A., E.W., A.N.), Care Sciences and Society, Center for Alzheimer Research, Division of Clinical Geriatrics, and Division of Neurogeriatrics (C.G.), Karolinska Institutet, Stockholm Department of Psychology (O.A.), Stockholm University; The Aging Brain Unit (O.A., A.N.) and Unit for Hereditary Dementias (C.G.), Theme Aging, Karolinska University Hospital, Stockholm; Department of Surgical Sciences, Section of Nuclear Medicine & PET (A.W.), Uppsala University, Sweden; and Department of Neuroimaging (E.W.), Centre for Neuroimaging Sciences, Institute of Psychiatry, Psychology and Neuroscience, King's College London, United Kingdom.

Juan Fortea (J)

From the Memory Unit, Department of Neurology (E.V., V.M., A.L., J.F.), Hospital de la Santa Creu i Sant Pau, Biomedical Research Institute Sant Pau, Universitat Autònoma de Barcelona; Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas, CIBERNED (E.V., V.M., A.L., J.F.), Madrid, Spain; Department of Neurobiology (E.R.-V., D.F., O.A., E.W., A.N.), Care Sciences and Society, Center for Alzheimer Research, Division of Clinical Geriatrics, and Division of Neurogeriatrics (C.G.), Karolinska Institutet, Stockholm Department of Psychology (O.A.), Stockholm University; The Aging Brain Unit (O.A., A.N.) and Unit for Hereditary Dementias (C.G.), Theme Aging, Karolinska University Hospital, Stockholm; Department of Surgical Sciences, Section of Nuclear Medicine & PET (A.W.), Uppsala University, Sweden; and Department of Neuroimaging (E.W.), Centre for Neuroimaging Sciences, Institute of Psychiatry, Psychology and Neuroscience, King's College London, United Kingdom.

Agneta Nordberg (A)

From the Memory Unit, Department of Neurology (E.V., V.M., A.L., J.F.), Hospital de la Santa Creu i Sant Pau, Biomedical Research Institute Sant Pau, Universitat Autònoma de Barcelona; Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas, CIBERNED (E.V., V.M., A.L., J.F.), Madrid, Spain; Department of Neurobiology (E.R.-V., D.F., O.A., E.W., A.N.), Care Sciences and Society, Center for Alzheimer Research, Division of Clinical Geriatrics, and Division of Neurogeriatrics (C.G.), Karolinska Institutet, Stockholm Department of Psychology (O.A.), Stockholm University; The Aging Brain Unit (O.A., A.N.) and Unit for Hereditary Dementias (C.G.), Theme Aging, Karolinska University Hospital, Stockholm; Department of Surgical Sciences, Section of Nuclear Medicine & PET (A.W.), Uppsala University, Sweden; and Department of Neuroimaging (E.W.), Centre for Neuroimaging Sciences, Institute of Psychiatry, Psychology and Neuroscience, King's College London, United Kingdom. Agneta.K.Nordberg@ki.se.
ORCID: 0000-0001-7345-5151

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Classifications MeSH

questionsmedicales.fr › Personnes › Tranches d'âge › Adulte › Cortical microstructural correlates of...
questionsmedicales.fr › Troubles mentaux › Troubles neurocognitifs › Démence › Maladie d'Alzheimer › Cortical microstructural correlates of...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines sécrétoires inhibitrices de protéinases › Protéase nexines › Précurseur de la protéine bêta-amyloïde › Cortical microstructural correlates of...
questionsmedicales.fr › Système nerveux › Système nerveux central › Encéphale › Cortical microstructural correlates of...
questionsmedicales.fr › Produits chimiques inorganiques › Isotopes › Radio-isotopes › Radio-isotopes du carbone › Cortical microstructural correlates of...
questionsmedicales.fr › Système nerveux › Système nerveux central › Encéphale › Prosencéphale › Télencéphale › Cerveau › Cortex cérébral › Cortical microstructural correlates of...
questionsmedicales.fr › Produits chimiques inorganiques › Isotopes › Deutérium › Cortical microstructural correlates of...
questionsmedicales.fr › Phénomènes génétiques › Génotype › Hétérozygote › Cortical microstructural correlates of...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Cortical microstructural correlates of...
questionsmedicales.fr › Diagnostic › Techniques et procédures diagnostiques › Imagerie diagnostique › Tomographie › Imagerie par résonance magnétique › Cortical microstructural correlates of...
questionsmedicales.fr › Personnes › Tranches d'âge › Adulte › Adulte d'âge moyen › Cortical microstructural correlates of...
questionsmedicales.fr › Phénomènes génétiques › Variation génétique › Mutation › Cortical microstructural correlates of...
questionsmedicales.fr › Techniques d'investigation › Neuroimagerie › Cortical microstructural correlates of...
questionsmedicales.fr › Disciplines et activités comportementales › Tests psychologiques › Tests neuropsychologiques › Cortical microstructural correlates of...
questionsmedicales.fr › Diagnostic › Techniques et procédures diagnostiques › Techniques de diagnostic radioisotopique › Scintigraphie › Tomoscintigraphie › Tomographie par émission de positons › Cortical microstructural correlates of...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines membranaires › Présénilines › Préséniline-1 › Cortical microstructural correlates of...
questionsmedicales.fr › Diagnostic › Symptômes prodromiques › Cortical microstructural correlates of...
questionsmedicales.fr › Composés chimiques organiques › Amines › Éthylamines › Phénéthylamines › Sélégiline › Cortical microstructural correlates of...