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[11C]Martinostat PET analysis reveals reduced HDAC I availability in Alzheimer’s disease

Author

Listed:
  • Tharick A. Pascoal

    (McGill University
    University of Pittsburgh School of Medicine
    University of Pittsburgh School of Medicine
    McGill University)

  • Mira Chamoun

    (McGill University)

  • Elad Lax

    (Ariel University
    McGill University)

  • Hsiao-Ying Wey

    (McGill University)

  • Monica Shin

    (McGill University)

  • Kok Pin Ng

    (McGill University)

  • Min Su Kang

    (McGill University
    McGill University)

  • Sulantha Mathotaarachchi

    (McGill University)

  • Andrea L. Benedet

    (McGill University)

  • Joseph Therriault

    (McGill University)

  • Firoza Z. Lussier

    (McGill University)

  • Frederick A. Schroeder

    (Harvard Medical School)

  • Jonathan M. DuBois

    (Harvard Medical School)

  • Baileigh G. Hightower

    (Harvard Medical School)

  • Tonya M. Gilbert

    (Harvard Medical School)

  • Nicole R. Zürcher

    (Harvard Medical School)

  • Changning Wang

    (Harvard Medical School)

  • Robert Hopewell

    (McGill University)

  • Mallar Chakravarty

    (Brain Imaging Centre)

  • Melissa Savard

    (McGill University)

  • Emilie Thomas

    (McGill University)

  • Sara Mohaddes

    (McGill University)

  • Sarah Farzin

    (Brain Imaging Centre)

  • Alyssa Salaciak

    (Brain Imaging Centre)

  • Stephanie Tullo

    (Brain Imaging Centre)

  • A. Claudio Cuello

    (McGill University)

  • Jean-Paul Soucy

    (McGill University)

  • Gassan Massarweh

    (McGill University)

  • Heungsun Hwang

    (McGill University)

  • Eliane Kobayashi

    (McGill University)

  • Bradley T. Hyman

    (Harvard Medical School)

  • Bradford C. Dickerson

    (Harvard Medical School
    McGill University)

  • Marie-Christine Guiot

    (McGill University)

  • Moshe Szyf

    (McGill University)

  • Serge Gauthier

    (McGill University)

  • Jacob M. Hooker

    (Harvard Medical School)

  • Pedro Rosa-Neto

    (McGill University
    McGill University)

Abstract

Alzheimer’s disease (AD) is characterized by the brain accumulation of amyloid-β 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-β and tau proteins. Using positron emission tomography (PET) tracers selective for amyloid-β, 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-β PET and tau PET concentrations. Notably, HDAC I reduction mediates the deleterious effects of amyloid-β 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-β 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.

Suggested Citation

  • Tharick A. Pascoal & Mira Chamoun & Elad Lax & Hsiao-Ying Wey & Monica Shin & Kok Pin Ng & Min Su Kang & Sulantha Mathotaarachchi & Andrea L. Benedet & Joseph Therriault & Firoza Z. Lussier & Frederic, 2022. "[11C]Martinostat PET analysis reveals reduced HDAC I availability in Alzheimer’s disease," Nature Communications, Nature, vol. 13(1), pages 1-11, December.
  • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-30653-5
    DOI: 10.1038/s41467-022-30653-5
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    References listed on IDEAS

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