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Alzheimer's Research & Therapy
Published in: Alzheimer's Research & Therapy 4/2014

Open Access 01-08-2014 | Review

Targeting the proper amyloid-beta neuronal toxins: a path forward for Alzheimer’s disease immunotherapeutics

Authors: William F Goure, Grant A Krafft, Jasna Jerecic, Franz Hefti

Published in: Alzheimer's Research & Therapy | Issue 4/2014

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Abstract

Levels of amyloid-beta monomer and deposited amyloid-beta in the Alzheimer’s disease brain are orders of magnitude greater than soluble amyloid-beta oligomer levels. Monomeric amyloid-beta has no known direct toxicity. Insoluble fibrillar amyloid-beta has been proposed to be an in vivo mechanism for removal of soluble amyloid-beta and exhibits relatively low toxicity. In contrast, soluble amyloid-beta oligomers are widely reported to be the most toxic amyloid-beta form, both causing acute synaptotoxicity and inducing neurodegenerative processes. None of the amyloid-beta immunotherapies currently in clinical development selectively target soluble amyloid-beta oligomers, and their lack of efficacy is not unexpected considering their selectivity for monomeric or fibrillar amyloid-beta (or both) rather than soluble amyloid-beta oligomers. Because they exhibit acute, memory-compromising synaptic toxicity and induce chronic neurodegenerative toxicity and because they exist at very low in vivo levels in the Alzheimer’s disease brain, soluble amyloid-beta oligomers constitute an optimal immunotherapeutic target that should be pursued more aggressively.
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Metadata
Title
Targeting the proper amyloid-beta neuronal toxins: a path forward for Alzheimer’s disease immunotherapeutics
Authors
William F Goure
Grant A Krafft
Jasna Jerecic
Franz Hefti
Publication date
01-08-2014
Publisher
BioMed Central
Published in
Alzheimer's Research & Therapy / Issue 4/2014
Electronic ISSN: 1758-9193
DOI
https://doi.org/10.1186/alzrt272

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