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Licensed Unlicensed Requires Authentication Published by De Gruyter August 15, 2019

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

Bryant Lim, Magda Tsolaki, Antoninus Soosaipillai, Marshall Brown, Maria Zilakaki, Fani Tagaraki, Dimitrios Fotiou, Effrosyni Koutsouraki, Effrosyni Grosi, Ioannis Prassas and Eleftherios P. Diamandis

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.


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

  1. 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.

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

  3. Employment or leadership: None declared.

  4. Honorarium: None declared.

  5. 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.

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

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Supplementary Material

The online version of this article offers supplementary material (https://doi.org/10.1515/cclm-2019-0428).


Received: 2019-05-02
Accepted: 2019-07-23
Published Online: 2019-08-15
Published in Print: 2019-11-26

©2019 Walter de Gruyter GmbH, Berlin/Boston

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