NeuroMolecular Medicine

, Volume 16, Issue 2, pp 405–414

Distinct Patterns of Sirtuin Expression During Progression of Alzheimer’s Disease

  • Mirjam I. Lutz
  • Ivan Milenkovic
  • Günther Regelsberger
  • Gabor G. Kovacs
Original Paper

DOI: 10.1007/s12017-014-8288-8

Cite this article as:
Lutz, M.I., Milenkovic, I., Regelsberger, G. et al. Neuromol Med (2014) 16: 405. doi:10.1007/s12017-014-8288-8

Abstract

Aging is one of the major risk factors for Alzheimer’s disease (AD). Sirtuins are associated with prolonged life span. To examine whether the expression levels of sirtuins associate with the progression of AD or not, we performed a comparative immunoblotting and immunohistochemical study of SIRT1, 3, and 5 in the entorhinal cortex and hippocampal subregions and white matter in 45 cases grouped according to Braak and Braak stages of neurofibrillary degeneration. In addition, we compared the expression levels with the local load of tau and amyloid-beta deposits, evaluated using morphometry. Our study revealed that (1) the neuronal subcellular redistribution of SIRT1 parallels the decrease in its expression, suggesting stepwise loss of neuroprotection dependent on the neuronal population; (2) in contrast to SIRT1 and 3, expression of SIRT5 increases during the progression of AD; (3) which might be related to its appearance in activated microglial cells. The complex patterns of the expression of sirtuins in relation to tissue damage should be taken into account when searching for therapies interacting with sirtuins.

Keywords

Aging Alzheimer’s disease Hippocampus Sirtuin SIRT1 SIRT3 SIRT5 

Supplementary material

12017_2014_8288_MOESM1_ESM.tif (6.8 mb)
Suppl.Fig. 1. Specificity control of SIRT1 and 5 antibodies. In comparison with the immunoreactivity of SIRT1 (a) and SIRT5 (c) antibody alone, the incubation with blocking peptide abolished immunolabeling in the tissue (b and d). (TIFF 6959 kb)

Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Mirjam I. Lutz
    • 1
  • Ivan Milenkovic
    • 1
  • Günther Regelsberger
    • 1
  • Gabor G. Kovacs
    • 1
  1. 1.Institute of NeurologyMedical University of ViennaViennaAustria

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