The Role of Amyloid-β Oligomers in Toxicity, Propagation, and Immunotherapy

Abstract

The incidence of Alzheimer's disease (AD) is growing every day and finding an effective treatment is becoming more vital. Amyloid-β (Aβ) has been the focus of research for several decades. The recent shift in the Aβ cascade hypothesis from all Aβ to small soluble oligomeric intermediates is directing the search for therapeutics towards the toxic mediators of the disease. Targeting the most toxic oligomers may prove to be an effective treatment by preventing their spread. Specific targeting of oligomers has been shown to protect cognition in rodent models. Additionally, the heterogeneity of research on Aβ oligomers may seem contradictory until size and conformation are taken into account. In this review, we will discuss Aβ oligomers and their toxicity in relation to size and conformation as well as their influence on inflammation and the potential of Aβ oligomer immunotherapy.

Highlights

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  An inverse correlation exists between oligomer size and toxicity after a critical mass is reached.

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  Protein aggregates propagate through prion-like mechanisms and preventing this propagation is possible through immunotherapy.

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  There may be an interplay between inflammation and oligomer induced toxicity and formation.