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Elife. 2017 Jun 26;6. pii: e28401. doi: 10.7554/eLife.28401.

Somatostatin binds to the human amyloid β peptide and favors the formation of distinct oligomers.

Author information

1
Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto, Toronto, Canada.
2
Molecular Medicine Program, Research Institute, The Hospital for Sick Children, Toronto, Canada.
3
Department of Medical Biophysics, University of Toronto, Toronto, Canada.
4
Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Canada.
5
Department of Biochemistry, University of Alberta, Edmonton, Canada.
6
Centre for Prions and Protein Folding Diseases, University of Alberta, Edmonton, Canada.
7
Department of Biochemistry, University of Toronto, Toronto, Canada.

Abstract

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.

KEYWORDS:

Alzheimer's disease; abeta; biochemistry; human; interactome; mass spectrometry; mouse; neuroscience; oligomer; somatostatin

PMID:
28650319
PMCID:
PMC5505701
DOI:
10.7554/eLife.28401
[Indexed for MEDLINE]
Free PMC Article

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