title: Brain cortical cholesterol metabolism is highly affected by human APP overexpression in mice.
abstract: Processing of the amyloid precursor protein (APP) and amyloid beta (Aβ) 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 Aβ 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 APPSL 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 APPSL 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 APPSL mice induces mechanisms to reduce free cholesterol levels.
authors.affiliation: QPS Austria, Parkring 12, 8074 Grambach, Austria. Electronic address: Tina.Loeffler@qps.com.
authors.forename: Tina
authors.initials: T
authors.lastname: Löffler
authors.affiliation: QPS Austria, Parkring 12, 8074 Grambach, Austria. Electronic address: Cornelia.Schweinzer@qps.com.
authors.forename: Cornelia
authors.initials: C
authors.lastname: Schweinzer
authors.affiliation: QPS Austria, Parkring 12, 8074 Grambach, Austria. Electronic address: Stefanie.Flunkert@qps.com.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Flunkert
authors.affiliation: Institute of Biochemistry, Biological Research Center of the Hungarian Academy of Sciences, Temesvári krt. 62, 6726 Szeged, Hungary. Electronic address: santha.miklos@gmail.com.
authors.forename: Miklós
authors.initials: M
authors.lastname: Sántha
authors.affiliation: NeuroScios GmbH, Willersdorferstrasse 6, 8061 St. Radegund, Austria. Electronic address: mwindisch@neuroscios.com.
authors.forename: Manfred
authors.initials: M
authors.lastname: Windisch
authors.affiliation: Institute of Molecular Biology and Biochemistry, Medical University Graz, Harrachgasse 21, 8010 Graz, Austria. Electronic address: ernst.steyrer@medunigraz.at.
authors.forename: Ernst
authors.initials: E
authors.lastname: Steyrer
authors.affiliation: QPS Austria, Parkring 12, 8074 Grambach, Austria. Electronic address: Birgit.Hutter-Paier@qps.com.
authors.forename: Birgit
authors.initials: B
authors.lastname: Hutter-Paier
mesh_terms: D000544:Alzheimer Disease / Q000097:blood / Q000235:genetics* / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D053299:Apolipoprotein B-100 / Q000235:genetics / Q000378:metabolism; D002540:Cerebral Cortex / Q000378:metabolism*; D002784:Cholesterol / Q000097:blood / Q000378:metabolism*; D059305:Diet, High-Fat / Q000009:adverse effects; D004041:Dietary Fats / Q000378:metabolism; D005260:Female; D005838:Genotype; D006706:Homeostasis; D006801:Humans; D008297:Male; D018782:Maze Learning; D051379:Mice; D008810:Mice, Inbred C57BL
chemical_list: C545487:APP protein, human; D016564:Amyloid beta-Protein Precursor; D053299:Apolipoprotein B-100; D004041:Dietary Fats; D002784:Cholesterol
keywords: APP(SL); Alzheimer's disease; Amyloid precursor protein overexpression; Aβ; Cholesterol; Mouse model