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Clathrin-mediated endocytic proteins are upregulated in the cortex of the Tg2576 mouse model of Alzheimer's disease-like amyloid pathology

Thomas, Rhian Sara, Lelos, Mariah Jillian ORCID:, Good, Mark Andrew ORCID: and Kidd, Emma Jane ORCID: 2011. Clathrin-mediated endocytic proteins are upregulated in the cortex of the Tg2576 mouse model of Alzheimer's disease-like amyloid pathology. Biochemical and Biophysical Research Communications 415 (4) , pp. 656-661. 10.1016/j.bbrc.2011.10.131

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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.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Pharmacy
Subjects: B Philosophy. Psychology. Religion > BF Psychology
R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry
R Medicine > RM Therapeutics. Pharmacology
Uncontrolled Keywords: AD, Alzheimer’s disease; Aβ, amyloid-β; APP, amyloid precursor protein; Wt, wild-type; Tg, transgenic; CME, clathrin-mediated endocytosis
Publisher: Elsevier
ISSN: 0006-291X
Last Modified: 03 Dec 2022 11:06

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