title: Clathrin-mediated endocytic proteins are upregulated in the cortex of the Tg2576 mouse model of Alzheimer's disease-like amyloid pathology.
abstract: Amyloid-β (Aβ) is cleaved from amyloid precursor protein (APP) predominantly after APP has trafficked through the secretory pathway and then become re-internalised by endocytosis. Clathrin-mediated and, more recently, clathrin-independent endocytosis have both been implicated in this process. Furthermore, endocytic abnormalities have been identified in cases of Alzheimer's disease (AD), however, the relevance of these changes to the aetiology of the disease remains unclear. We therefore examined the expression of proteins related to these endocytic processes in the cortex of Tg2576 mice that overexpress the Swedish mutation in APP, and consequently overexpress Aβ, to determine if there were any changes in their associated pathways. We identified significant increases in the levels of clathrin, dynamin and PICALM, all proteins intimately involved with the clathrin-mediated endocytic pathway, in the transgenic animals. However, levels of proteins associated with flotillin or caveolin-mediated endocytic pathways remained unchanged. These results emphasise the importance of clathrin-mediated endocytosis in the aetiology of AD and reinforce the results of the recent GWAS studies that identified genes for clathrin-mediated endocytosis as susceptibility genes for AD. Such studies in transgenic mice will allow us to learn more about the role of clathrin-mediated endocytosis in AD.
authors.affiliation: Welsh School of Pharmacy, Cardiff University, Redwood Building, King Edward VII Avenue, Cardiff CF10 3NB, UK. Thomasrs2@cf.ac.uk
authors.forename: Rhian S
authors.initials: RS
authors.lastname: Thomas
authors.forename: Mariah J
authors.initials: MJ
authors.lastname: Lelos
authors.forename: Mark A
authors.initials: MA
authors.lastname: Good
authors.forename: Emma J
authors.initials: EJ
authors.lastname: Kidd
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism; D000818:Animals; D051242:Caveolin 1 / Q000235:genetics / Q000378:metabolism; D051244:Caveolin 3 / Q000235:genetics / Q000378:metabolism; D002540:Cerebral Cortex / Q000378:metabolism*; D002966:Clathrin / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D004705:Endocytosis / Q000235:genetics*; D055106:Genome-Wide Association Study; D051379:Mice; D008822:Mice, Transgenic; D015854:Up-Regulation
chemical_list: D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D051242:Caveolin 1; D051244:Caveolin 3; D002966:Clathrin