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. © 2014 Goure et al.; licensee BioMed Central Ltd.
CITATION STYLE
Goure, W. F., Krafft, G. A., Jerecic, J., & Hefti, F. (2014, July 9). Targeting the proper amyloid-beta neuronal toxins: A path forward for Alzheimer’s disease immunotherapeutics. Alzheimer’s Research and Therapy. BioMed Central Ltd. https://doi.org/10.1186/alzrt272
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