Berson_2008_Brain_131_109

Reference

Title : Changes in readthrough acetylcholinesterase expression modulate amyloid-beta pathology - Berson_2008_Brain_131_109
Author(s) : Berson A , Knobloch M , Hanan M , Diamant S , Sharoni M , Schuppli D , Geyer BC , Ravid R , Mor TS , Nitsch RM , Soreq H
Ref : Brain , 131 :109 , 2008
Abstract :

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.

PubMedSearch : Berson_2008_Brain_131_109
PubMedID: 18056160

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Citations formats

Berson A, Knobloch M, Hanan M, Diamant S, Sharoni M, Schuppli D, Geyer BC, Ravid R, Mor TS, Nitsch RM, Soreq H (2008)
Changes in readthrough acetylcholinesterase expression modulate amyloid-beta pathology
Brain 131 :109

Berson A, Knobloch M, Hanan M, Diamant S, Sharoni M, Schuppli D, Geyer BC, Ravid R, Mor TS, Nitsch RM, Soreq H (2008)
Brain 131 :109