Author response: Somatostatin binds to the human amyloid β peptide and favors the formation of distinct oligomers

Abstract

The amyloid b peptide (Ab) is a key player in the etiology of Alzheimer disease (AD), yet a systematic investigation of its molecular interactions has not been reported. Here we identified by quantitative mass spectrometry proteins in human brain extract that bind to oligomeric Ab1-42 (oAb1-42) and/or monomeric Ab1-42 (mAb1-42) baits. Remarkably, the cyclic neuroendocrine peptide somatostatin-14 (SST14) was observed to be the most selectively enriched oAb1-42 binder. The binding interface comprises a central tryptophan within SST14 and the N-terminus of Ab1-42. The presence of SST14 inhibited Ab aggregation and masked the ability of several antibodies to detect Ab. Notably, Ab1-42, but not Ab1-40, formed in the presence of SST14 oligomeric assemblies of 50 to 60 kDa that were visualized by gel electrophoresis, nanoparticle tracking analysis and electron microscopy. These findings may be relevant for Abdirected diagnostics and may signify a role of SST14 in the etiology of AD.