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Acetylcholinesterase is increased in the brains of transgenic mice expressing the C-terminal fragment (CT100) of the beta-amyloid protein precursor of Alzheimer's disease

journal contribution
posted on 2023-05-17, 10:02 authored by Sberna, G, Saez-Valero, J, Li, QX, Czech, C, Beyreuther, K, Masters, CL, McLean, CA, David SmallDavid Small
Acetylcholinesterase (AChE) expression is markedly affected in Alzheimer's disease (AD). AChE activity is lower in most regions of the AD brain, but it is increased within and around amyloid plaques. We have previously shown that AChE expression in P19 cells is increased by the amyloid β protein (Aβ). The aim of this study was to investigate AChE expression using a transgenic mouse model of Aβ overproduction. The β-actin promoter was used to drive expression of a transgene encoding the 100-amino acid C-terminal fragment of the human amyloid precursor protein (APP CT100). Analysis of extracts from transgenic mice revealed that the human sequences of full-length human APP CT100 and Aβ were overexpressed in the brain. Levels of salt-extractable AChE isoforms were increased in the brains of APP CT100 mice. There was also an increase in amphiphilic monomeric form (GA1) of AChE in the APP CT100 mice, whereas other isoforms were not changed. An increase in the proportion of GA1 AChE was also detected in samples of frontal cortex from AD patients. Analysis of AChE by lectin binding revealed differences in the glycosylation pattern in APP CT100 mice similar to those observed in frontal cortex samples from AD. The results are consistent with the possibility that changes in AChE isoform levels and glycosylation patterns in the AD brain may be a direct consequence of altered APP metabolism.

History

Publication title

Journal of Neurochemistry

Volume

71

Pagination

723-731

ISSN

0022-3042

Department/School

Menzies Institute for Medical Research

Publisher

Blackwell Publishing Ltd

Place of publication

9600 Garsington Rd, Oxford, England, Oxon, Ox4 2Dg

Rights statement

The definitive published version is available online at: http://www3.interscience.wiley.com/

Repository Status

  • Restricted

Socio-economic Objectives

Clinical health not elsewhere classified

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