Quick Search:

uzh logo
Browse by:

Zurich Open Repository and Archive

Maintenance: Tuesday, 5.7.2016, 07:00-08:00

Maintenance work on ZORA and JDB on Tuesday, 5th July, 07h00-08h00. During this time there will be a brief unavailability for about 1 hour. Please be patient.

Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-7239

Berson, A; Knobloch, M; Hanan, M; Diamant, S; Sharoni, M; Schuppli, D; Geyer, B C; Ravid, R; Mor, T S; Nitsch, R M; Soreq, H (2008). Changes in readthrough acetylcholinesterase expression modulate amyloid-beta pathology. Brain: A Journal of Neurology, 131(1):109-119.

[img] PDF - Registered users only
View at publisher


Alzheimer's disease has long been known to involve cholinergic deficits, but the linkage between cholinergic gene expression and the Alzheimer's disease amyloid pathology has remained incompletely understood. One known link involves synaptic acetylcholinesterase (AChE-S), shown to accelerate amyloid fibrils formation. Here, we report that the 'Readthrough' AChE-R splice variant, which differs from AChE-S in its 26 C-terminal residues, inversely exerts neuroprotective effects from amyloid beta (Abeta) induced toxicity. In vitro, highly purified AChE-R dose-dependently suppressed the formation of insoluble Abeta oligomers and fibrils and abolished Abeta toxicity to cultured cells, competing with the prevalent AChE-S protein which facilitates these processes. In vivo, double transgenic APPsw/AChE-R mice showed lower plaque burden, fewer reactive astrocytes and less dendritic damage than single APPsw mice, inverse to reported acceleration of these features in double APPsw/AChE-S mice. In hippocampi from Alzheimer's disease patients (n = 10), dentate gyrus neurons showed significantly elevated AChE-R mRNA and reduced AChE-S mRNA. However, immunoblot analyses revealed drastic reductions in the levels of intact AChE-R protein, suggesting that its selective loss in the Alzheimer's disease brain exacerbates the Abeta-induced damages and revealing a previously unforeseen linkage between cholinergic and amyloidogenic events.


62 citations in Web of Science®
66 citations in Scopus®
Google Scholar™



1 download since deposited on 29 Dec 2008
0 downloads since 12 months

Detailed statistics

Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Psychiatric University Hospital Zurich > Division of Psychiatric Research and Clinic for Psychogeriatric Medicine
Dewey Decimal Classification:610 Medicine & health
Deposited On:29 Dec 2008 12:22
Last Modified:05 Apr 2016 12:39
Publisher:Oxford University Press
Publisher DOI:10.1093/brain/awm276
Related URLs:http://brain.oxfordjournals.org/ (Publisher)
PubMed ID:18056160

Users (please log in): suggest update or correction for this item

Repository Staff Only: item control page