Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto, Toronto, Canada
Lisa D Muiznieks
Molecular Medicine Program, Research Institute, The Hospital for Sick Children, Toronto, Canada
Punam Ghosh
Department of Medical Biophysics, University of Toronto, Toronto, Canada
Declan Williams
Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto, Toronto, Canada
Michael Solarski
Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto, Toronto, Canada; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Canada
Andrew Fang
Department of Biochemistry, University of Alberta, Edmonton, Canada; Centre for Prions and Protein Folding Diseases, University of Alberta, Edmonton, Canada
Molecular Medicine Program, Research Institute, The Hospital for Sick Children, Toronto, Canada; Department of Biochemistry, University of Toronto, Toronto, Canada
Joel C Watts
Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto, Toronto, Canada; Department of Biochemistry, University of Toronto, Toronto, Canada
Avi Chakrabartty
Department of Medical Biophysics, University of Toronto, Toronto, Canada; Department of Biochemistry, University of Toronto, Toronto, Canada
Department of Biochemistry, University of Alberta, Edmonton, Canada; Centre for Prions and Protein Folding Diseases, University of Alberta, Edmonton, Canada
Simon Sharpe
Molecular Medicine Program, Research Institute, The Hospital for Sick Children, Toronto, Canada; Department of Biochemistry, University of Toronto, Toronto, Canada
Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto, Toronto, Canada; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Canada
The amyloid β peptide (Aβ) 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 Aβ1-42 (oAβ1-42) and/or monomeric Aβ1-42 (mAβ1-42) baits. Remarkably, the cyclic neuroendocrine peptide somatostatin-14 (SST14) was observed to be the most selectively enriched oAβ1-42 binder. The binding interface comprises a central tryptophan within SST14 and the N-terminus of Aβ1-42. The presence of SST14 inhibited Aβ aggregation and masked the ability of several antibodies to detect Aβ. Notably, Aβ1-42, but not Aβ1-40, 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 Aβ-directed diagnostics and may signify a role of SST14 in the etiology of AD.
