Protein Array Based Interactome Analysis of Amyloid-β Indicates an Inhibition of Protein Translation

Oligomeric amyloid-P is currently of interest in amyloid-P mediated toxicity and the pathogenesis of Alzheimer's disease. Mapping the amyloid-beta interaction partners could help to discover novel pathways in disease pathogenesis. To discover the amyloid-beta interaction partners, we applied a protein array with more than 8100 unique recombinantly expressed human proteins. We identified 324 proteins as potential interactors of oligomeric amyloid-P. The Gene Ontology functional analysis of these proteins showed that oligomeric amyloid-beta bound to multiple proteins with diverse functions both from extra and intracellular localizations. This undiscriminating binding phenotype indicates that multiple protein interactions mediate the toxicity of the oligomeric amyloid-beta. The most highly impacted cellular system was the protein translation machinery. Oligomeric amyloid-beta could bind to altogether 24 proteins involved in translation initiation and elongation. The binding of amyloid-beta to purified rat hippocampal ribosomes validated the protein array results. More importantly, in vitro translation assays showed that the oligomeric amyloid-beta had a concentration dependent inhibitory activity on translation. Our results indicate that the inhibited protein synthesis is one of the pathways that can be involved in the amyloid-beta induced neurotoxicity.