Sirtuin 1 reduction parallels the accumulation of tau in Alzheimer disease.
J Neuropathol Exp Neurol
; 68(1): 48-58, 2009 Jan.
Article
en En
| MEDLINE
| ID: mdl-19104446
ABSTRACT
Aging and metabolism-related disorders are risk factors for Alzheimer disease (AD). Because sirtuins may increase the life span through regulation of cellular metabolism, we compared the concentration of sirtuin 1 (SIRT1) in the brains of AD patients (n = 19) and controls (n = 22) using Western immunoblots and in situ hybridization. We report a significant reduction of SIRT1 (messenger RNA [mRNA], -29%; protein, -45%) in the parietal cortex of AD patients, but not in the cerebellum. Further analyses in a second cohort of 36 subjects confirmed that cortical SIRT1 was decreased in AD but not in individuals with mild cognitive impairment. SIRT1 mRNA and its translated protein correlated negatively with the duration of symptoms (mRNA, r2 = -0.367; protein, r2 = -0.326) and the accumulation of paired helical filament tau (mRNA, r2 = -0.230; protein, r2 = -0.119), but weakly with insoluble amyloid-beta 42 (mRNA, r2= -0.090; protein, r2 = -0.072). A significant relationship between SIRT1 levels and global cognition scores proximate to death was also found (r2= +0.09, p = 0.049). In contrast, cortical SIRT1 levels remained unchanged in a triple-transgenic animal model of AD. Collectively, our results indicate that loss of SIRT1 is closely associated with the accumulation of amyloid-beta and tau in the cerebral cortex of persons with AD.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Regulación de la Expresión Génica
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Proteínas tau
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Sirtuinas
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Enfermedad de Alzheimer
Tipo de estudio:
Etiology_studies
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Incidence_studies
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Observational_studies
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Prognostic_studies
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Risk_factors_studies
Límite:
Aged
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Animals
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
J Neuropathol Exp Neurol
Año:
2009
Tipo del documento:
Article
País de afiliación:
Canadá