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Altered glycosylation of acetylcholinesterase in APP (SW) Tg2576 transgenic mice occurs prior to amyloid plaque deposition

journal contribution
posted on 2023-05-17, 09:59 authored by Fodero, LR, Saez-Valero, J, McLean, CA, Martins, RN, Beyreuther, K, Masters, CL, Robertson, TA, David SmallDavid Small
Previous studies have shown that a minor glycoform of acetylcholinesterase (AChE) is increased in Alzheimer's disease brain and cerebrospinal fluid. This glycoform can be distinguished from other AChE species by its lack of binding to concanavalin A (Con A). In this study, the temporal relationship between AChE glycosylation and Aβ deposition was examined in Tg2576 mice. There was a significant (p < 0.05) difference in AChE glycosylation in Tg2576 mice compared with age-matched background strain control mice at 4 months of age. This difference in glycosylation was also observed in 8- and 12-month-old Tg2576 mice. In contrast, Aβ plaques were only seen in the Tg2576 mice at 12 months of age, and were not detected at 4 and 8 months of age. Soluble human-sequence Aβ was detected as early as 4 months of age in the transgenic mice. The altered AChE glycosylation was due to an increase in a minor AChE isoform, which did not bind Con A, similar to that previously observed to be increased in Alzheimer's disease brain and cerebrospinal fluid. The results demonstrate that in transgenic mice altered AChE glycosylation is associated with very early events in the development of AD-like pathology. The study supports the possibility that glycosylation may also be a useful biomarker of AD.

History

Publication title

Journal of Neurochemistry

Volume

81

Pagination

441-448

ISSN

0022-3042

Department/School

Menzies Institute for Medical Research

Publisher

Wiley-Blackwell

Place of publication

United Kingdom

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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