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Publication : Exercise is more effective than diet control in preventing high fat diet-induced β-amyloid deposition and memory deficit in amyloid precursor protein transgenic mice.

First Author  Maesako M Year  2012
Journal  J Biol Chem Volume  287
Issue  27 Pages  23024-33
PubMed ID  22563077 Mgi Jnum  J:188380
Mgi Id  MGI:5440391 Doi  10.1074/jbc.M112.367011
Citation  Maesako M, et al. (2012) Exercise is more effective than diet control in preventing high fat diet-induced beta-amyloid deposition and memory deficit in amyloid precursor protein transgenic mice. J Biol Chem 287(27):23024-33
abstractText  Accumulating evidence suggests that some dietary patterns, specifically high fat diet (HFD), increase the risk of developing sporadic Alzheimer disease (AD). Thus, interventions targeting HFD-induced metabolic dysfunctions may be effective in preventing the development of AD. We previously demonstrated that amyloid precursor protein (APP)-overexpressing transgenic mice fed HFD showed worsening of cognitive function when compared with control APP mice on normal diet. Moreover, we reported that voluntary exercise ameliorates HFD-induced memory impairment and beta-amyloid (Abeta) deposition. In the present study, we conducted diet control to ameliorate the metabolic abnormality caused by HFD on APP transgenic mice and compared the effect of diet control on cognitive function with that of voluntary exercise as well as that of combined (diet control plus exercise) treatment. Surprisingly, we found that exercise was more effective than diet control, although both exercise and diet control ameliorated HFD-induced memory deficit and Abeta deposition. The production of Abeta was not different between the exercise- and the diet control-treated mice. On the other hand, exercise specifically strengthened the activity of neprilysin, the Abeta-degrading enzyme, the level of which was significantly correlated with that of deposited Abeta in our mice. Notably, the effect of the combination treatment (exercise and diet control) on memory and amyloid pathology was not significantly different from that of exercise alone. These studies provide solid evidence that exercise is a useful intervention to rescue HFD-induced aggravation of cognitive decline in transgenic model mice of AD.
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