Distinct patterns of sirtuin expression during progression of Alzheimer's disease.
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.
Institute of Neurology, Medical University of Vienna, AKH 4 J, Währinger Gürtel 18-20, 1097, Vienna, Austria.
Mirjam I
MI
Lutz
Ivan
I
Milenkovic
Günther
G
Regelsberger
Gabor G
GG
Kovacs
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000032:analysis; D018450:Disease Progression; D018728:Entorhinal Cortex / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005786:Gene Expression Regulation; D006624:Hippocampus / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000096:biosynthesis* / Q000235:genetics; D009474:Neurons / Q000737:chemistry / Q000473:pathology; D056564:Sirtuin 1 / Q000096:biosynthesis* / Q000235:genetics; D056566:Sirtuin 3 / Q000096:biosynthesis* / Q000235:genetics; D037761:Sirtuins / Q000096:biosynthesis* / Q000235:genetics; D013347:Subcellular Fractions / Q000737:chemistry; D066127:White Matter / Q000378:metabolism* / Q000473:pathology; D016875:tau Proteins / Q000032:analysis
D016229:Amyloid beta-Peptides; C054369:MAPT protein, human; D009419:Nerve Tissue Proteins; D016875:tau Proteins; C447939:SIRT1 protein, human; C466093:SIRT3 protein, human; C508544:SIRT5 protein, human; D056564:Sirtuin 1; D056566:Sirtuin 3; D037761:Sirtuins