A novel quantification-driven proteomic strategy identifies an endogenous peptide of pleiotrophin as a new biomarker of Alzheimer’s disease
Open accessAbstract
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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Elevated PTN is detected in the substantia nigra of patients with Parkinson's disease and in the CSF of patients with AD.
“Elevated PTN is detected in the substantia nigra of patients with Parkinson's disease and in the cerebrospinal fluid (CSF) of patients with AD. 41 , 42”
From Loss of <i>Inpp5d</i> has disease‐relevant and sex‐specific effects on glial transcriptomes (2024) · cites this paper as [42]
The Results (Validation of PTN 151–166 as a biomarker of AD; page unavailable) report elevated CSF levels in AD patients, supporting the AD portion of the sentence. The measured substance was the PTN 151–166 peptide, not full-length PTN; the paper does not establish elevated PTN in the substantia nigra of patients with Parkinson’s disease. (LLM, conf=0.86)
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- Authors
- Skillbäck, T., Mattsson, N., Hansson, K., Mirgorodskaya, E., Dahlén, R., van der Flier, W., Scheltens, P., Duits, F., Hansson, O., Teunissen, C., Blennow, K., Zetterberg, H., & Gobom, J.
- Affiliations
- Sahlgrenska University Hospital (SE)
- Lund University (SE)
- University of Gothenburg (SE)
- Amsterdam Neuroscience (NL)
- Corresponding author
- Gobom, Johan
- ORCID
- Venue
- Scientific Reports
- Published
- 2017-10-17
- Volume
- 7
- Issue
- 1
- Pages
- 13333-13333
- ISSN
- 2045-2322 (ISSN-L)
- PMC
- PMC5645330
- OpenAlex
- W2763859909
- Cited by
- 61
- References
- 58
- Citations by year
- 2026: 2 · 2025: 7 · 2024: 7 · 2023: 5 · 2022: 2 · 2021: 3 · 2020: 28 · 2019: 2 · 2018: 4
- FWCI
- 4.59
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Scientific Reports (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Amsterdam UMC (VU Amsterdam) - Institutional Repository (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Lund University Publications (Lund University) (submittedVersion)
- Pure Amsterdam UMC (submittedVersion, cc-by)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Funders
- Torsten Söderbergs Stiftelse
- Demensförbundet
- Lunds Universitet
- Knut och Alice Wallenbergs Stiftelse
- Vetenskapsrådet
- Sahlgrenska Universitetssjukhuset
- Magnus Bergvalls Stiftelse
- Alzheimerfonden
- Emil och Wera Cornells Stiftelse
- Parkinsonfonden
- Topics
- Physical Sciences › Chemistry › Spectroscopy › Advanced Proteomics Techniques and Applications
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- Alzheimer's disease, biomarker discovery, pleiotrophin, cerebrospinal fluid, spectral clustering, isobaric labeling, mild cognitive impairment, Parkinson's disease, progressive supranuclear palsy, peptide fragments
- MeSH terms
- Alzheimer Disease, Carrier Proteins, Female, Humans, Male, Peptides, ROC Curve, Reproducibility of Results, Biomarkers, Cytokines, Proteome, Proteomics
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