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Updated: Jun 16, 2026

An Alternative Approach to Study Primary Events in Neurodegeneration Using Ex Vivo Rat Brain Slices
Published on: April 11, 2018
Acetylcholinesterase variants in Alzheimer's disease: from neuroprotection to programmed cell death
David S Greenberg1, Debra Toiber, Amit Berson
1Department of Biological Chemistry, The Hebrew University of Jerusalem, Safra Campus, Givat Ram, Jerusalem, Israel.
Background:
In Alzheimer's disease (AD), cholinergic neurons are particularly vulnerable for as yet unclear reasons. Here, we report that modified composition, localization and properties of alternative splice variants encoding the acetylcholine-hydrolyzing enzyme acetylcholinesterase (AChE) may be variably involved in disease progression or in systemic efforts to attenuate its progression.
Objective:
The purpose of this study was to explore the implications for AD of the cellular and biochemical properties of the various AChE proteins, differing in their N and C termini.
Methods:
We have used cell transfection with genetically engineered vectors as well as microinjection to overexpress specific AChE variants and explore the consequences to cellular well-being and survival. Additionally, we employed highly purified recombinant AChE-R and AChE-S to explore putative interactions with the AD beta-amyloid peptide.
Results:
Our findings demonstrate distinct, and in certain cases inverse cell fate outcome under enforced expression of the human N- and C-terminally modified AChE variants, all of which have similar enzymatic activities.
Conclusion:
The N-terminal extension in conjunction with the primary helical C-terminal peptide of 'tailed' AChE-S facilitates, whereas the shorter, naturally unfolded C-terminus of the stress-induced AChE-R variant attenuates Alzheimer's pathology.
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