Aβ oligomer-induced synapse degeneration in Alzheimer's disease - PubMed (original) (raw)

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Aβ oligomer-induced synapse degeneration in Alzheimer's disease

Kyle C Wilcox et al. Cell Mol Neurobiol. 2011 Aug.

Abstract

Aβ oligomers cause a collection of molecular events associated with memory loss in Alzheimer's disease, centering on disrupting the maintenance of synapse structure and function. In this brief review of the synaptotoxic effects of Aβ oligomers, we focus on the neuronal properties governing oligomer targeting and toxicity-especially with respect to binding sites and mechanisms of binding. We also discuss ways in which mechanistic insights from other diseases offer clues in the pursuit of the molecular basis of Alzheimer's disease.

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Fig. 1

Fig. 1

Formation and synaptic targeting of Aβ oligomers. A neuron is represented with blue neurites and red dendritic spines (background image). Following APP cleavage at the neural membrane by β- and γ-secretase, the 42-residue Aβ peptide (red) can be deposited into senile plaques or can alternatively form a collection of oligomeric species (left inset). Some component of this collection of oligomers interacts with neurons to form synaptic clusters which are associated with a variety of synaptic pathologies including the internalization of receptors involved in synapse function and maintenance and the initiation of toxic signaling cascades (right inset)

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