期刊
MOLECULAR AND CELLULAR NEUROSCIENCE
卷 74, 期 -, 页码 34-41出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.mcn.2016.03.004
关键词
Alzheimer's disease; A beta; Cholesterol; Amyloid precursor protein overexpression; Mouse model; APP(SL)
资金
- Franz-Lanyar-Stiftung [372]
- Institute of Molecular Biology and Biochemistry (Medical University of Graz)
- QPS Austria
Processing of the amyloid precursor protein (APP) and amyloid beta (A beta) has been for decades in the center of Alzheimer's disease (AD) research. Beside many other variables, lipids, especially cholesterol and its derivatives, are discussed to contribute to AD pathogenesis. Several studies show that cholesterol affects APP metabolism. Also the converse mechanism, the direct influence of A beta on cholesterol metabolism, has been described. To further investigate this crosstalk between cholesterol- and APP metabolism, a high-fat feeding study was conducted with animals overexpressing human APP(SL) and/or human ApoB-100. The impact of diet and genotype on cerebral cholesterol metabolism and content as well as spatial learning and memory was examined. While behavioral performance was not influenced by this high fat diet (HFD), reduction of cortical free cholesterol levels and mRNA expression patterns under normal diet and HFD conditions in human APP(SL) overexpressing mice argue for an important role of APP in cerebral lipid metabolism. From our results we conclude that increased APP metabolism in ApoBxAPP and APP(SL) mice induces mechanisms to reduce free cholesterol levels. (C) 2016 Elsevier Inc. All rights reserved.
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