Reduced expression of SIRT1 and SOD-1 and the correlation between these levels in various regions of the brains of patients with Alzheimer's disease

J Clin Pathol. 2018 Dec;71(12):1090-1099. doi: 10.1136/jclinpath-2018-205320. Epub 2018 Sep 5.

Abstract

Aims: This study was designed to explore the expression and distribution of silent information regulator 1 (SIRT1) and superoxide dismutase 1 (SOD-1) in various regions of the brains of patients with Alzheimer's disease (AD), as well as to assess potential correlations between the levels of these proteins and also between these proteins and the Braak stage of AD.

Methods: In the temporal and frontal cortices, hippocampus and cerebellum of 10 patients with AD and 10 age-matched control subjects, expression of SIRT1 and SOD-1, together with histopathology, were assessed by immunohistochemical and immunofluorescent stainings. Relationships between variables were examined with the Pearson correlation test.

Results: The numbers of both SIRT1-positive and SOD-1-positive neurons and integrated optical density of immunohistochemical staining for these proteins in the temporal and frontal cortices, and hippocampus of patients with AD were significantly decreased than those in corresponding controls. In the case of the cerebellum, very weak expression of SIRT1 and obvious expression of SOD-1 were observed in granule cells, with no significant difference between AD and the control group. Interestingly, the protein levels between SIRT1 and SOD-1, as well as the level of SIRT1 or SOD-1 and Braak stage, were significantly correlated in neurons in all regions of the AD brains investigated except for the cerebellum.

Conclusions: These findings indicate that the reduced level of SIRT1 in the brains of patients with AD may be related to the decline in SOD-1 and neuropathological changes of this disorder.

Keywords: Alzheimer's disease; SIRT1; SOD-1; brains; patient.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alzheimer Disease / metabolism
  • Alzheimer Disease / pathology*
  • Brain / metabolism
  • Brain / pathology
  • Case-Control Studies
  • Female
  • Fluorescent Antibody Technique
  • Humans
  • Immunohistochemistry
  • Male
  • Oxidative Stress
  • Sirtuin 1 / metabolism*
  • Superoxide Dismutase-1 / metabolism*

Substances

  • SOD1 protein, human
  • Superoxide Dismutase-1
  • SIRT1 protein, human
  • Sirtuin 1