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Clinical Chemistry and Laboratory Medicine (CCLM)

Published in Association with the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM)

Editor-in-Chief: Plebani, Mario

Ed. by Gillery, Philippe / Greaves, Ronda / Lackner, Karl J. / Lippi, Giuseppe / Melichar, Bohuslav / Payne, Deborah A. / Schlattmann, Peter


IMPACT FACTOR 2018: 3.638

CiteScore 2018: 2.44

SCImago Journal Rank (SJR) 2018: 1.191
Source Normalized Impact per Paper (SNIP) 2018: 1.205

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1437-4331
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Volume 57, Issue 12

Issues

Liquid biopsy of cerebrospinal fluid identifies neuronal pentraxin receptor (NPTXR) as a biomarker of progression of Alzheimer’s disease

Bryant Lim / Magda Tsolaki
  • Corresponding author
  • 1st Department of Neurology, Medical School, Aristotle University of Thessaloniki, Thessaloniki, Greece
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/ Antoninus Soosaipillai
  • Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, ON M5T 3L9, Canada
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/ Marshall Brown / Maria Zilakaki
  • 1st Department of Neurology, Medical School, Aristotle University of Thessaloniki, Thessaloniki, Greece
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/ Fani Tagaraki
  • 1st Department of Neurology, Medical School, Aristotle University of Thessaloniki, Thessaloniki, Greece
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/ Dimitrios Fotiou
  • 1st Department of Neurology, Medical School, Aristotle University of Thessaloniki, Thessaloniki, Greece
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/ Effrosyni Koutsouraki
  • 1st Department of Neurology, Medical School, Aristotle University of Thessaloniki, Thessaloniki, Greece
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/ Effrosyni Grosi
  • 1st Department of Neurology, Medical School, Aristotle University of Thessaloniki, Thessaloniki, Greece
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/ Ioannis Prassas
  • Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, ON M5T 3L9, Canada
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/ Eleftherios P. Diamandis
  • Corresponding author
  • Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Canada
  • Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, ON M5T 3L9, Canada
  • Department of Clinical Biochemistry, University Health Network, Toronto, ON, Canada
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Published Online: 2019-08-15 | DOI: https://doi.org/10.1515/cclm-2019-0428

Abstract

Background

Alzheimer’s disease (AD) is the most prevalent form of dementia. Currently, the most studied biomarkers of AD are cerebrospinal fluid (CSF) amyloid β 1-42, total tau and phosphorylated tau. However, misdiagnosis can exceed 20%. Recently, we found that CSF amyloid β precursor-like protein-1 (APLP1) and neuronal pentraxin receptor (NPTXR) are promising biomarkers of AD. The aim of the present study is to validate CSF APLP1 and NPTXR as biomarkers of AD severity.

Methods

APLP1 and NPTXR concentrations were measured in the CSF of patients with mild cognitive impairment (MCI) (n = 14), mild AD (n = 21), moderate AD (n = 43) and severe AD (n = 30) using enzyme-linked immunosorbent assays (ELISAs).

Results

CSF APLP1 and NPTXR were not associated with age or sex. CSF APLP1 was not different between any of the AD severity groups (p = 0.31). CSF NPTXR was significantly different between MCI and mild AD (p = 0.006), mild and moderate AD (p = 0.016), but not between moderate and severe AD (p = 0.36). NPTXR concentration progressively declined from MCI to mild, to moderate and to severe AD patients (p < 0.0001, Kruskal-Wallis test). CSF NPTXR positively correlated with the Mini-Mental Status Examination (MMSE) score (p < 0.001).

Conclusions

NPTXR concentration in CSF is a promising biomarker of AD severity and could inform treatment success and disease progression in clinical settings.

This article offers supplementary material which is provided at the end of the article.

Keywords: Alzheimer’s disease; Alzheimer’s disease progression; amyloid precursor-like protein-1; biomarkers; cerebrospinal fluid; dementia; neuronal pentraxin receptor

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About the article

Corresponding authors: Magda Tsolaki, PhD, MD, 1st Department of Neurology, Medical School, Aristotle University of Thessaloniki, Thessaloniki, Greece; and Eleftherios P. Diamandis, PhD, MD, Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Canada; Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, 60 Murray St [Box 32], Flr 6 – Rm L6-201-1, Toronto, ON M5T 3L9, Canada; and Department of Clinical Biochemistry, University Health Network, Toronto, ON, Canada, Phone: +416-586-8443, Fax: +416-619-5521


Received: 2019-05-02

Accepted: 2019-07-23

Published Online: 2019-08-15

Published in Print: 2019-11-26


Author contributions: Bryant Lim: participated in data acquisition, analysis and interpretation, and drafted the manuscript. Magda Tsolaki, Maria Zilakaki, Fani Tagaraki, Dimitrios Fotiou, Effrosyni Koutsouraki, Effrosyni Grosi: collected patient samples and clinical information. Antoninus Soosaipillai: participated in data collection. Marshall Brown: participated in data analysis and statistics. Ioannis Prassas: participated in study conception and design. Eleftherios Diamandis: supervised the study, participated in conception and design and provided funding. All authors participated in manuscript revision and editing and approved the final form. All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.

Research funding: Funding was provided by the Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, Canada.

Employment or leadership: None declared.

Honorarium: None declared.

Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.

Availability of data and materials: The datasets used and/or analyzed during the current study are available from the corresponding author upon request.


Citation Information: Clinical Chemistry and Laboratory Medicine (CCLM), Volume 57, Issue 12, Pages 1875–1881, ISSN (Online) 1437-4331, ISSN (Print) 1434-6621, DOI: https://doi.org/10.1515/cclm-2019-0428.

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