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

Amyloid-beta (Ap) 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 Ap generation. We compared protein expression in frontal cortex samples from men with AD compared to age-matched, non-diseased controls. Soluble and insoluble Ap40 and Ap42, the soluble Ap42/Ap40 ratio, pCTF, BACE1, presenilin-1 and the ratio of phospho-rylated:total GSK3p were significantly increased while the insoluble Ap42:Ap40 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 sug-gest an overall increase in endocytosis in the AD brain, explaining, at least in part, the increased production of Ap during AD.(c) 2023 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY -NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).