Upregulation of endocytic protein expression in the Alzheimer's disease male human brain

Alsaqati, Mouhamed, Thomas, Rhian S. and Kidd, Emma J. ORCID: https://orcid.org/0000-0001-5507-1170 2023. Upregulation of endocytic protein expression in the Alzheimer's disease male human brain. Aging Brain 4 , 100084. 10.1016/j.nbas.2023.100084

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Abstract

Amyloid-beta (Aβ) is produced from amyloid precursor protein (APP) primarily after APP is internalised by endocytosis and clathrin-mediated endocytic processes are altered in Alzheimer’s disease (AD). There is also evidence that cholesterol and flotillin affect APP endocytosis. We hypothesised that endocytic protein expression would be altered in the brains of people with AD compared to non-diseased subjects which could be linked to increased Aβ generation. We compared protein expression in frontal cortex samples from men with AD compared to age-matched, non-diseased controls. Soluble and insoluble Aβ40 and Aβ42, the soluble Aβ42/Aβ40 ratio, βCTF, BACE1, presenilin-1 and the ratio of phosphorylated:total GSK3β were significantly increased while the insoluble Aβ42:Aβ40 ratio was significantly decreased in AD brains. Total and phosphorylated tau were markedly increased in AD brains. Significant increases in clathrin, AP2, PICALM isoform 4, Rab-5 and caveolin-1 and 2 were seen in AD brains but BIN1 was decreased. However, using immunohistochemistry, caveolin-1 and 2 were decreased. The results obtained here suggest an overall increase in endocytosis in the AD brain, explaining, at least in part, the increased production of Aβ during AD

Item Type:	Article
Date Type:	Published Online
Status:	Published
Schools:	Pharmacy
Publisher:	Elsevier
ISSN:	2589-9589
Date of First Compliant Deposit:	3 July 2023
Date of Acceptance:	16 June 2023
Last Modified:	05 Jul 2023 07:17
URI:	https://orca.cardiff.ac.uk/id/eprint/160784

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