Proteins involved in endocytosis are upregulated by ageing in the normal human brain: implications for the development of Alzheimer's disease

Alsaqati, Mouhamed, Thomas, Rhian S. and Kidd, Emma ORCID: https://orcid.org/0000-0001-5507-1170 2017. Proteins involved in endocytosis are upregulated by ageing in the normal human brain: implications for the development of Alzheimer's disease. Journals of Gerontology, Series A 73 (3) , pp. 289-298. 10.1093/gerona/glx135

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Abstract

The greatest risk factor for Alzheimer’s disease (AD) is advanced age, but the reason for this association remains unclear. Amyloid-beta (Aβ) is produced from amyloid precursor protein (APP) primarily after APP is internalised by clathrin-mediated or clathrin-independent endocytosis. Changes in endocytosis in AD have been identified. We hypothesised that endocytic protein expression is altered during ageing, thus influencing the likelihood of developing AD by increasing Aβ production. We explored how levels of endocytic proteins, APP, its metabolites, secretase enzymes and tau varied with age in cortical brain samples from men of three age ranges (young (20–30), middle-aged (45–55) and old (70–90)) with no symptoms of dementia. Aβ40 and Aβ42 were significantly increased in old brains, while APP and secretase expression was unaffected by age. Phosphorylated GSK3β increased significantly with age, a possible precursor for neurofibrillary tangle production, although phosphorylated tau was undetectable. Significant increases in clathrin, dynamin-1, AP180, Rab-5, caveolin-2 and flotillin-2 were seen in old brains. Rab-5 also increased in middle-aged brains prior to changes in Aβ levels. This age-related increase in endocytic protein expression, not described previously, suggests an age-related up-regulation of endocytosis which could predispose older individuals to develop AD by increasing APP internalisation and Aβ generation.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Pharmacy
Subjects:	R Medicine > RS Pharmacy and materia medica
Uncontrolled Keywords:	Age, amyloid precursor protein, amyloid-beta, human brain.
Publisher:	Oxford University Press (OUP): Policy B - Oxford Open Option D
ISSN:	1079-5006
Date of First Compliant Deposit:	27 June 2017
Date of Acceptance:	18 June 2017
Last Modified:	06 Nov 2024 02:00
URI:	https://orca.cardiff.ac.uk/id/eprint/101777

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