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

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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.

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Acknowledgments

The authors thank Irene Leisser, Gerda Ricken, and Eva Dassler for technical assistance and Dr. Thomas Ströbel for technical advice. This study was supported by DEVELAGE, a 7th framework program (FP7/2007-2013) under Grant Agreement No. 278486.

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The authors declare that they have no conflict of interest.

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  1. Institute of Neurology, Medical University of Vienna, AKH 4 J, Währinger Gürtel 18-20, 1097, Vienna, Austria

    Mirjam I. Lutz, Ivan Milenkovic, Günther Regelsberger & Gabor G. Kovacs

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  1. Mirjam I. Lutz
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  2. Ivan Milenkovic
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  3. Günther Regelsberger
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  4. Gabor G. Kovacs
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Correspondence to Gabor G. Kovacs.

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12017_2014_8288_MOESM1_ESM.tif

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)

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Lutz, M.I., Milenkovic, I., Regelsberger, G. et al. Distinct Patterns of Sirtuin Expression During Progression of Alzheimer’s Disease. Neuromol Med 16, 405–414 (2014). https://doi.org/10.1007/s12017-014-8288-8

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