[11C]Martinostat PET analysis reveals reduced HDAC I availability in Alzheimer's disease.
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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Histona Desacetilase 1
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Doença de Alzheimer
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Disfunção Cognitiva
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article