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

Mouhamed Alsaqati, Rhian Thomas Orcid Logo, Emma J. Kidd Orcid Logo

Aging Brain, Volume: 4, Start page: 100084

Swansea University Author: Rhian Thomas Orcid Logo

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DOI (Published version): 10.1016/j.nbas.2023.100084

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...

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Published in: Aging Brain
ISSN: 2589-9589
Published: Elsevier BV 2023
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URI: https://cronfa.swan.ac.uk/Record/cronfa63878
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spelling v2 63878 2023-07-13 Upregulation of endocytic protein expression in the Alzheimer’s disease male human brain 10f33f117e548cddfa6758ea130c3407 0000-0002-7286-2764 Rhian Thomas Rhian Thomas true false 2023-07-13 PHAR 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. Journal Article Aging Brain 4 100084 Elsevier BV 2589-9589 Alzheimer’s disease, Amyloid precursor protein, Amyloid-beta, Endocytosis, Human brain, Male sex 21 6 2023 2023-06-21 10.1016/j.nbas.2023.100084 http://dx.doi.org/10.1016/j.nbas.2023.100084 COLLEGE NANME Pharmacy COLLEGE CODE PHAR Swansea University This work and MA were supported by Bristol Research into Alzheimer's and Care of Elderly (BRACE). The authors would like to thank Prof. Peter Davies for the gift of the PHF-1 antibody. The authors gratefully acknowledge the Newcastle Brain Tissue Resource which provided the brain samples for this study. The Resource is funded in part by a grant from the UK Medical Research Council (G0400074), by NIHR Newcastle Biomedical Research Centre and Unit awarded to the Newcastle upon Tyne NHS Foundation Trust and Newcastle University, and by a grant from Alzheimer's Society and Alzheimer's Research Trust as part of the Brains for Dementia Research Project. 2023-08-24T09:11:25.4618050 2023-07-13T11:46:15.1764573 Faculty of Medicine, Health and Life Sciences Swansea University Medical School - Pharmacy Mouhamed Alsaqati 1 Rhian Thomas 0000-0002-7286-2764 2 Emma J. Kidd 0000-0001-5507-1170 3 63878__28369__3a81b5ee651f46eebfb0ae9a50265217.pdf 63878.VOR.pdf 2023-08-24T09:09:05.5543943 Output 1770290 application/pdf Version of Record true © 2023 The Authors. Published by Elsevier Inc. Distributed under the terms of a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND 4.0). true eng https://creativecommons.org/licenses/by-nc-nd/4.0/
title Upregulation of endocytic protein expression in the Alzheimer’s disease male human brain
spellingShingle Upregulation of endocytic protein expression in the Alzheimer’s disease male human brain
Rhian Thomas
title_short Upregulation of endocytic protein expression in the Alzheimer’s disease male human brain
title_full Upregulation of endocytic protein expression in the Alzheimer’s disease male human brain
title_fullStr Upregulation of endocytic protein expression in the Alzheimer’s disease male human brain
title_full_unstemmed Upregulation of endocytic protein expression in the Alzheimer’s disease male human brain
title_sort Upregulation of endocytic protein expression in the Alzheimer’s disease male human brain
author_id_str_mv 10f33f117e548cddfa6758ea130c3407
author_id_fullname_str_mv 10f33f117e548cddfa6758ea130c3407_***_Rhian Thomas
author Rhian Thomas
author2 Mouhamed Alsaqati
Rhian Thomas
Emma J. Kidd
format Journal article
container_title Aging Brain
container_volume 4
container_start_page 100084
publishDate 2023
institution Swansea University
issn 2589-9589
doi_str_mv 10.1016/j.nbas.2023.100084
publisher Elsevier BV
college_str Faculty of Medicine, Health and Life Sciences
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hierarchy_top_title Faculty of Medicine, Health and Life Sciences
hierarchy_parent_id facultyofmedicinehealthandlifesciences
hierarchy_parent_title Faculty of Medicine, Health and Life Sciences
department_str Swansea University Medical School - Pharmacy{{{_:::_}}}Faculty of Medicine, Health and Life Sciences{{{_:::_}}}Swansea University Medical School - Pharmacy
url http://dx.doi.org/10.1016/j.nbas.2023.100084
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description 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.
published_date 2023-06-21T09:11:26Z
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