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Altered expression of brain acetylcholinesterase in FTDP-17 human tau transgenic mice

journal contribution
posted on 2023-05-17, 11:32 authored by Silveyra, M-X, Garcia-Ayllon, M-S, de Barreda, EG, David SmallDavid Small, Martinez, S, Avila, J, Saez-Valero, J
Pathological hyperphosphorylation and aggregation of the tau protein is associated with dementia and can be the central cause of neurodegeneration. Here, we examined potential alterations in the level of the cholinergic enzyme acetylcholinesterase (AChE) in the brain of transgenic mice (Tg-VLW) expressing human tau mutations. Overexpression of mutant hyperphosphorylated tau (P-tau) led to an increase in the activity of AChE in the brain of Tg-VLW mice, paralleled by an increase in AChE protein and transcripts; whereas the levels of the enzyme choline acetyltransferase remained unaffected. VLW tau overexpression in SH-SY5Y cells also increased AChE activity levels. All major molecular forms of AChE were increased in the Tg-VLW mice, including tetrameric AChE, which is the major species involved in hydrolysis of acetylcholine in the brain. Colocalization of human P-tau and AChE supports the conclusion that P-tau can act to increase AChE. This study is the first direct evidence of a modulatory effect of P-tau on brain AChE expression.

History

Publication title

Neurobiology of Aging: Experimental and Clinical Research

Volume

33

Pagination

624.e23- 624.e34

ISSN

0197-4580

Department/School

Menzies Institute for Medical Research

Publisher

Elsevier Science Inc

Place of publication

360 Park Ave South, New York, USA, Ny, 10010-1710

Rights statement

Copyright 2012 Elsevier

Repository Status

  • Restricted

Socio-economic Objectives

Clinical health not elsewhere classified

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