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

  • Bryant Lim , Magda Tsolaki EMAIL logo , Antoninus Soosaipillai , Marshall Brown , Maria Zilakaki , Fani Tagaraki , Dimitrios Fotiou , Effrosyni Koutsouraki , Effrosyni Grosi , Ioannis Prassas and Eleftherios P. Diamandis EMAIL logo
Published/Copyright: August 15, 2019
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Clinical Chemistry and Laboratory Medicine (CCLM)
From the journal Clinical Chemistry and Laboratory Medicine (CCLM) Volume 57 Issue 12

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.

Keywords: Alzheimer’s disease; Alzheimer’s disease progression; amyloid precursor-like protein-1; biomarkers; cerebrospinal fluid; dementia; neuronal pentraxin receptor
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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https://doi.org/10.1515/cclm-2019-0428
Keywords for this article
Alzheimer’s disease; Alzheimer’s disease progression; amyloid precursor-like protein-1; biomarkers; cerebrospinal fluid; dementia; neuronal pentraxin receptor

Articles in the same Issue

  1. Frontmatter
  2. Editorial
  3. The re-emergence of dried blood spot sampling – are we ready?
  4. Review
  5. The role of platelets in bleeding in patients with thrombocytopenia and hematological disease
  6. Opinion Paper
  7. Exertional hematuria: definition, epidemiology, diagnostic and clinical considerations
  8. Guidelines and Recommendations from Scientific Societies
  9. A protocol for testing the stability of biochemical analytes. Technical document
  10. Genetics and Molecular Diagnostics
  11. Hereditary hyperferritinaemia-cataract syndrome (HHCS) – an underestimated condition: ferritin light chain variant spectrum in German families
  12. General Clinical Chemistry and Laboratory Medicine
  13. Performance of a web-based application measuring spot quality in dried blood spot sampling
  14. Clinical application of a dried blood spot assay for sirolimus and everolimus in transplant patients
  15. Plasma and dried blood spot lysosphingolipids for the diagnosis of different sphingolipidoses: a comparative study
  16. Liquid biopsy of cerebrospinal fluid identifies neuronal pentraxin receptor (NPTXR) as a biomarker of progression of Alzheimer’s disease
  17. Integrity of serum samples is changed by modified centrifugation conditions
  18. Heparin and citrate additive carryover during blood collection
  19. Copeptin – a biomarker of short-term mortality risk (7 days) in patients with end-stage liver disease
  20. Comparison of a new rapid method for the determination of adalimumab serum levels with two established ELISA kits
  21. Measurement of α-dicarbonyl compounds in human saliva by pre-column derivatization HPLC
  22. Establishment of the intelligent verification criteria for a routine urinalysis analyzer in a multi-center study
  23. Reference Values and Biological Variations
  24. A new indirect estimation of reference intervals: truncated minimum chi-square (TMC) approach
  25. EGFR and EGFR ligands in serum in healthy women; reference intervals and age dependency
  26. Early pregnancy reference intervals; 29 serum analytes from 4 to 12 weeks’ gestation in naturally conceived and uncomplicated pregnancies resulting in live births
  27. Paediatric reference intervals for 17 Roche cobas 8000 e602 immunoassays in the CALIPER cohort of healthy children and adolescents
  28. Hematology and Coagulation
  29. Study of the analytical performance at different concentrations of hematological parameters using Spanish EQAS data
  30. Multicenter performance evaluation of the Abbott Alinity hq hematology analyzer
  31. Cardiovascular Diseases
  32. Fast 0/1-h algorithm for detection of NSTEMI: are current high-sensitivity cardiac troponin assays fit for purpose? An EQA-based evaluation
  33. Infectious Diseases
  34. Diagnostic performance of cerebrospinal fluid free light chains in Lyme neuroborreliosis – a pilot study
  35. Letters to the Editor
  36. Quality management at the national biobanking level – establishing a culture of mutual trust and support: the BBMRI.at example
  37. Molecular diagnosis of MODY3 permitted to reveal a de novo 12q24.31 deletion and to explain a complex phenotype in a young diabetic patient
  38. Increased C-reactive protein values in the absence of inflammation: monoclonal immunoglobulin interference in immunonephelometry
  39. An approach based on simulated hemolysis for establishing the hemolysis index threshold for high-sensitivity cardiac troponin T assay
  40. Utility of the icteric index for the management of bilirubin test requesting
  41. Quality control of monocyte volume and distribution width parameters of the Beckman Coulter DxH series
  42. Mozhaisk haemoglobin variant effects on leukocyte differential channel using the Sysmex XN series
  43. Detection of a novel hemoglobin variant Hb Liaoning by matrix assisted laser desorption/ionization-time of flight mass spectrometry
  44. Appropriateness of repetitive therapeutic drug monitoring and laboratory turnaround time
  45. Congress Abstracts
  46. 51th National Congress of the Italian Society of Clinical Biochemistry and Clinical Molecular Biology (SIBioC – Laboratory Medicine)
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