Potential Utility of Cerebrospinal Fluid Glycoprotein Nonmetastatic Melanoma Protein B as a Neuroinflammatory Diagnostic Biomarker in Mild Cognitive Impairment and Alzheimer’s Disease

Alzheimer’s disease (AD) is a very common neurodegenerative disorder characterized by the gradual loss of neurons and extracellular amyloid-peptide buildup. There is compelling evidence that the disease process depends on neuroinflammatory alterations, such as the activation of astrocytes and microg...

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Main Authors: Julia Doroszkiewicz, Agnieszka Kulczyńska-Przybik, Maciej Dulewicz, Renata Borawska, Monika Zajkowska, Agnieszka Słowik, Barbara Mroczko
Format: Article
Language:English
Published: MDPI AG 2023-07-01
Series:Journal of Clinical Medicine
Subjects:
Online Access:https://www.mdpi.com/2077-0383/12/14/4689
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author Julia Doroszkiewicz
Agnieszka Kulczyńska-Przybik
Maciej Dulewicz
Renata Borawska
Monika Zajkowska
Agnieszka Słowik
Barbara Mroczko
author_facet Julia Doroszkiewicz
Agnieszka Kulczyńska-Przybik
Maciej Dulewicz
Renata Borawska
Monika Zajkowska
Agnieszka Słowik
Barbara Mroczko
author_sort Julia Doroszkiewicz
collection DOAJ
description Alzheimer’s disease (AD) is a very common neurodegenerative disorder characterized by the gradual loss of neurons and extracellular amyloid-peptide buildup. There is compelling evidence that the disease process depends on neuroinflammatory alterations, such as the activation of astrocytes and microglia cells. A transmembrane glycoprotein known as glycoprotein nonmetastatic melanoma protein B (GPNMB) plays a neuroprotective role during the development of neurodegeneration. To the best of our knowledge, this is the first investigation discussing the potential clinical usefulness of this protein in the AD continuum, especially in the MCI (mild cognitive impairment) stage. A total of 71 patients with AD or MCI as well as controls were enrolled in this study. The concentrations of GPNMB, YKL-40, Aβ1-42 (amyloid beta 1-42), Tau, and pTau and the Aβ1-42/1-40 ratio in the CSF (cerebrospinal fluid) were tested using immunological methods. The concentrations of both GPNMB and YKL-40 in the cerebrospinal fluid were significantly higher in patients with AD and MCI compared to the controls. Moreover, both proteins were biochemically associated with classical biomarkers of AD and were especially associated with the Aβ1-42/1-40 ratio and Tau and pTau levels in the whole study group. Elevated concentrations of GPNMB were observed in the Aβ(+) group of AD patients compared to the Aβ(−) subjects. Additionally, the diagnostic performance (AUC value) of GPNMB was higher than that of amyloid β1-42 in MCI patients compared with controls. Our study indicates that GPNMB might be a promising neuroinflammatory biomarker for the early diagnosis and prognosis of the AD continuum, with potential utility as a therapeutic target.
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spelling doaj.art-ae35e27150dd433f8b8adcc3177676622023-11-18T19:52:30ZengMDPI AGJournal of Clinical Medicine2077-03832023-07-011214468910.3390/jcm12144689Potential Utility of Cerebrospinal Fluid Glycoprotein Nonmetastatic Melanoma Protein B as a Neuroinflammatory Diagnostic Biomarker in Mild Cognitive Impairment and Alzheimer’s DiseaseJulia Doroszkiewicz0Agnieszka Kulczyńska-Przybik1Maciej Dulewicz2Renata Borawska3Monika Zajkowska4Agnieszka Słowik5Barbara Mroczko6Department of Neurodegeneration Diagnostics, Medical University of Bialystok, 15-269 Bialystok, PolandDepartment of Neurodegeneration Diagnostics, Medical University of Bialystok, 15-269 Bialystok, PolandDepartment of Neurodegeneration Diagnostics, Medical University of Bialystok, 15-269 Bialystok, PolandDepartment of Neurodegeneration Diagnostics, Medical University of Bialystok, 15-269 Bialystok, PolandDepartment of Neurodegeneration Diagnostics, Medical University of Bialystok, 15-269 Bialystok, PolandDepartment of Neurology, Jagiellonian University, 30-688 Cracow, PolandDepartment of Neurodegeneration Diagnostics, Medical University of Bialystok, 15-269 Bialystok, PolandAlzheimer’s disease (AD) is a very common neurodegenerative disorder characterized by the gradual loss of neurons and extracellular amyloid-peptide buildup. There is compelling evidence that the disease process depends on neuroinflammatory alterations, such as the activation of astrocytes and microglia cells. A transmembrane glycoprotein known as glycoprotein nonmetastatic melanoma protein B (GPNMB) plays a neuroprotective role during the development of neurodegeneration. To the best of our knowledge, this is the first investigation discussing the potential clinical usefulness of this protein in the AD continuum, especially in the MCI (mild cognitive impairment) stage. A total of 71 patients with AD or MCI as well as controls were enrolled in this study. The concentrations of GPNMB, YKL-40, Aβ1-42 (amyloid beta 1-42), Tau, and pTau and the Aβ1-42/1-40 ratio in the CSF (cerebrospinal fluid) were tested using immunological methods. The concentrations of both GPNMB and YKL-40 in the cerebrospinal fluid were significantly higher in patients with AD and MCI compared to the controls. Moreover, both proteins were biochemically associated with classical biomarkers of AD and were especially associated with the Aβ1-42/1-40 ratio and Tau and pTau levels in the whole study group. Elevated concentrations of GPNMB were observed in the Aβ(+) group of AD patients compared to the Aβ(−) subjects. Additionally, the diagnostic performance (AUC value) of GPNMB was higher than that of amyloid β1-42 in MCI patients compared with controls. Our study indicates that GPNMB might be a promising neuroinflammatory biomarker for the early diagnosis and prognosis of the AD continuum, with potential utility as a therapeutic target.https://www.mdpi.com/2077-0383/12/14/4689Alzheimer’s diseaseGPNMBYKL-40neuroinflammation
spellingShingle Julia Doroszkiewicz
Agnieszka Kulczyńska-Przybik
Maciej Dulewicz
Renata Borawska
Monika Zajkowska
Agnieszka Słowik
Barbara Mroczko
Potential Utility of Cerebrospinal Fluid Glycoprotein Nonmetastatic Melanoma Protein B as a Neuroinflammatory Diagnostic Biomarker in Mild Cognitive Impairment and Alzheimer’s Disease
Journal of Clinical Medicine
Alzheimer’s disease
GPNMB
YKL-40
neuroinflammation
title Potential Utility of Cerebrospinal Fluid Glycoprotein Nonmetastatic Melanoma Protein B as a Neuroinflammatory Diagnostic Biomarker in Mild Cognitive Impairment and Alzheimer’s Disease
title_full Potential Utility of Cerebrospinal Fluid Glycoprotein Nonmetastatic Melanoma Protein B as a Neuroinflammatory Diagnostic Biomarker in Mild Cognitive Impairment and Alzheimer’s Disease
title_fullStr Potential Utility of Cerebrospinal Fluid Glycoprotein Nonmetastatic Melanoma Protein B as a Neuroinflammatory Diagnostic Biomarker in Mild Cognitive Impairment and Alzheimer’s Disease
title_full_unstemmed Potential Utility of Cerebrospinal Fluid Glycoprotein Nonmetastatic Melanoma Protein B as a Neuroinflammatory Diagnostic Biomarker in Mild Cognitive Impairment and Alzheimer’s Disease
title_short Potential Utility of Cerebrospinal Fluid Glycoprotein Nonmetastatic Melanoma Protein B as a Neuroinflammatory Diagnostic Biomarker in Mild Cognitive Impairment and Alzheimer’s Disease
title_sort potential utility of cerebrospinal fluid glycoprotein nonmetastatic melanoma protein b as a neuroinflammatory diagnostic biomarker in mild cognitive impairment and alzheimer s disease
topic Alzheimer’s disease
GPNMB
YKL-40
neuroinflammation
url https://www.mdpi.com/2077-0383/12/14/4689
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