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Upregulation of endocytic protein expression in the Alzheimer’s disease male human brain
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Emma J. Kidd
Aging Brain, Volume: 4, Start page: 100084
Swansea University Author:
Rhian Thomas
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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...
| Published in: | Aging Brain |
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| ISSN: | 2589-9589 |
| Published: |
Elsevier BV
2023
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| Online Access: |
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| URI: | https://cronfa.swan.ac.uk/Record/cronfa63878 |
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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. |
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| Keywords: |
Alzheimer’s disease, Amyloid precursor protein, Amyloid-beta, Endocytosis, Human brain, Male sex |
| College: |
Faculty of Medicine, Health and Life Sciences |
| Funders: |
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. |
| Start Page: |
100084 |