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[11C]Martinostat PET analysis reveals reduced HDAC I availability in Alzheimer's disease.
Pascoal, Tharick A; Chamoun, Mira; Lax, Elad; Wey, Hsiao-Ying; Shin, Monica; Ng, Kok Pin; Kang, Min Su; Mathotaarachchi, Sulantha; Benedet, Andrea L; Therriault, Joseph; Lussier, Firoza Z; Schroeder, Frederick A; DuBois, Jonathan M; Hightower, Baileigh G; Gilbert, Tonya M; Zürcher, Nicole R; Wang, Changning; Hopewell, Robert; Chakravarty, Mallar; Savard, Melissa; Thomas, Emilie; Mohaddes, Sara; Farzin, Sarah; Salaciak, Alyssa; Tullo, Stephanie; Cuello, A Claudio; Soucy, Jean-Paul; Massarweh, Gassan; Hwang, Heungsun; Kobayashi, Eliane; Hyman, Bradley T; Dickerson, Bradford C; Guiot, Marie-Christine; Szyf, Moshe; Gauthier, Serge; Hooker, Jacob M; Rosa-Neto, Pedro.
Afiliação
  • Pascoal TA; Translational Neuroimaging Laboratory, Department of Neurology and Neurosurgery, Faculty of Medicine, The McGill University Research Centre for Studies in Aging, McGill University, Montreal, QC, Canada.
  • Chamoun M; Departments of Psychiatry and Neurology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
  • Lax E; Departments of Neurology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
  • Wey HY; Montreal Neurological Institute, McGill University, Montreal, QC, Canada.
  • Shin M; Translational Neuroimaging Laboratory, Department of Neurology and Neurosurgery, Faculty of Medicine, The McGill University Research Centre for Studies in Aging, McGill University, Montreal, QC, Canada.
  • Ng KP; Department of Molecular Biology, Ariel University, Ariel, Israel.
  • Kang MS; Department of Pharmacology and Therapeutics, McGill University, Montreal, QC, Canada.
  • Mathotaarachchi S; Department of Pharmacology and Therapeutics, McGill University, Montreal, QC, Canada.
  • Benedet AL; Translational Neuroimaging Laboratory, Department of Neurology and Neurosurgery, Faculty of Medicine, The McGill University Research Centre for Studies in Aging, McGill University, Montreal, QC, Canada.
  • Therriault J; Translational Neuroimaging Laboratory, Department of Neurology and Neurosurgery, Faculty of Medicine, The McGill University Research Centre for Studies in Aging, McGill University, Montreal, QC, Canada.
  • Lussier FZ; Translational Neuroimaging Laboratory, Department of Neurology and Neurosurgery, Faculty of Medicine, The McGill University Research Centre for Studies in Aging, McGill University, Montreal, QC, Canada.
  • Schroeder FA; Montreal Neurological Institute, McGill University, Montreal, QC, Canada.
  • DuBois JM; Translational Neuroimaging Laboratory, Department of Neurology and Neurosurgery, Faculty of Medicine, The McGill University Research Centre for Studies in Aging, McGill University, Montreal, QC, Canada.
  • Hightower BG; Translational Neuroimaging Laboratory, Department of Neurology and Neurosurgery, Faculty of Medicine, The McGill University Research Centre for Studies in Aging, McGill University, Montreal, QC, Canada.
  • Gilbert TM; Translational Neuroimaging Laboratory, Department of Neurology and Neurosurgery, Faculty of Medicine, The McGill University Research Centre for Studies in Aging, McGill University, Montreal, QC, Canada.
  • Zürcher NR; Translational Neuroimaging Laboratory, Department of Neurology and Neurosurgery, Faculty of Medicine, The McGill University Research Centre for Studies in Aging, McGill University, Montreal, QC, Canada.
  • Wang C; Neurology Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA.
  • Hopewell R; Neurology Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA.
  • Chakravarty M; Neurology Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA.
  • Savard M; Neurology Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA.
  • Thomas E; Neurology Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA.
  • Mohaddes S; Neurology Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA.
  • Farzin S; Montreal Neurological Institute, McGill University, Montreal, QC, Canada.
  • Salaciak A; Departments of Biological and Biomedical Engineering and Psychiatry, Douglas Mental Health University Institute, Brain Imaging Centre, Montreal, QC, Canada.
  • Tullo S; Translational Neuroimaging Laboratory, Department of Neurology and Neurosurgery, Faculty of Medicine, The McGill University Research Centre for Studies in Aging, McGill University, Montreal, QC, Canada.
  • Cuello AC; Translational Neuroimaging Laboratory, Department of Neurology and Neurosurgery, Faculty of Medicine, The McGill University Research Centre for Studies in Aging, McGill University, Montreal, QC, Canada.
  • Soucy JP; Translational Neuroimaging Laboratory, Department of Neurology and Neurosurgery, Faculty of Medicine, The McGill University Research Centre for Studies in Aging, McGill University, Montreal, QC, Canada.
  • Massarweh G; Departments of Biological and Biomedical Engineering and Psychiatry, Douglas Mental Health University Institute, Brain Imaging Centre, Montreal, QC, Canada.
  • Hwang H; Departments of Biological and Biomedical Engineering and Psychiatry, Douglas Mental Health University Institute, Brain Imaging Centre, Montreal, QC, Canada.
  • Kobayashi E; Departments of Biological and Biomedical Engineering and Psychiatry, Douglas Mental Health University Institute, Brain Imaging Centre, Montreal, QC, Canada.
  • Hyman BT; Department of Pharmacology and Therapeutics, McGill University, Montreal, QC, Canada.
  • Dickerson BC; Montreal Neurological Institute, McGill University, Montreal, QC, Canada.
  • Guiot MC; Montreal Neurological Institute, McGill University, Montreal, QC, Canada.
  • Szyf M; Department of Psychology, McGill University, Montreal, QC, Canada.
  • Gauthier S; Montreal Neurological Institute, McGill University, Montreal, QC, Canada.
  • Hooker JM; Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
  • Rosa-Neto P; Neurology Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA.
Nat Commun ; 13(1): 4171, 2022 07 19.
Article em En | MEDLINE | ID: mdl-35853847
ABSTRACT
Alzheimer's disease (AD) is characterized by the brain accumulation of amyloid-ß and tau proteins. A growing body of literature suggests that epigenetic dysregulations play a role in the interplay of hallmark proteinopathies with neurodegeneration and cognitive impairment. Here, we aim to characterize an epigenetic dysregulation associated with the brain deposition of amyloid-ß and tau proteins. Using positron emission tomography (PET) tracers selective for amyloid-ß, tau, and class I histone deacetylase (HDAC I isoforms 1-3), we find that HDAC I levels are reduced in patients with AD. HDAC I PET reduction is associated with elevated amyloid-ß PET and tau PET concentrations. Notably, HDAC I reduction mediates the deleterious effects of amyloid-ß and tau on brain atrophy and cognitive impairment. HDAC I PET reduction is associated with 2-year longitudinal neurodegeneration and cognitive decline. We also find HDAC I reduction in the postmortem brain tissue of patients with AD and in a transgenic rat model expressing human amyloid-ß plus tau pathology in the same brain regions identified in vivo using PET. These observations highlight HDAC I reduction as an element associated with AD pathophysiology.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Histona Desacetilase 1 / Doença de Alzheimer / Disfunção Cognitiva Idioma: En Ano de publicação: 2022 Tipo de documento: Article
Texto completo
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Histona Desacetilase 1 / Doença de Alzheimer / Disfunção Cognitiva Idioma: En Ano de publicação: 2022 Tipo de documento: Article