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Sci Rep. 2017 Oct 17;7(1):13333. doi: 10.1038/s41598-017-13831-0.

A novel quantification-driven proteomic strategy identifies an endogenous peptide of pleiotrophin as a new biomarker of Alzheimer's disease.

Author information

1
Institute of Neuroscience and Physiology, Department of Neurochemistry, the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.
2
Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden.
3
Clinical Memory Research Unit, Department of Clinical Sciences Malmö, Lund University, Malmö, Sweden.
4
Department of Neurology, Skåne University Hospital, Lund, Sweden.
5
Proteomics Core Facility, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
6
Alzheimer Centre, Amsterdam Neuroscience, VU University Medical Center, Amsterdam, The Netherlands.
7
Department of Molecular Neuroscience, UCL Institute of Neurology, Queen Square, London, UK.
8
Institute of Neuroscience and Physiology, Department of Neurochemistry, the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden. johan.gobom@neuro.gu.se.
9
Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden. johan.gobom@neuro.gu.se.

Abstract

We present a new, quantification-driven proteomic approach to identifying biomarkers. In contrast to the identification-driven approach, limited in scope to peptides that are identified by database searching in the first step, all MS data are considered to select biomarker candidates. The endopeptidome of cerebrospinal fluid from 40 Alzheimer's disease (AD) patients, 40 subjects with mild cognitive impairment, and 40 controls with subjective cognitive decline was analyzed using multiplex isobaric labeling. Spectral clustering was used to match MS/MS spectra. The top biomarker candidate cluster (215% higher in AD compared to controls, area under ROC curve = 0.96) was identified as a fragment of pleiotrophin located near the protein's C-terminus. Analysis of another cohort (n = 60 over four clinical groups) verified that the biomarker was increased in AD patients while no change in controls, Parkinson's disease or progressive supranuclear palsy was observed. The identification of the novel biomarker pleiotrophin 151-166 demonstrates that our quantification-driven proteomic approach is a promising method for biomarker discovery, which may be universally applicable in clinical proteomics.

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