The cerebrospinal fluid Glycoprotein Nonmetastatic Melanoma Protein B (GPNMB) concentration in Alzheimer’s Disease (AD)

Abstract

Background: Alzheimer Disease (AD) is a common neurodegenerative disorder which is the most widespread form of dementia in the world. The disease is characterized by amyloid-β peptides, phosphorylated tau proteins and neuroinflammation. Because of late manifestation of the disease, it is pivotal to find new biomarkers that can help detect AD in the earliest phases. Glycoprotein nonmetastatic melanoma protein B (GPNMB) is a transmembrane endogenous glycoprotein involved in neuroinflammation. Recent studies have confirmed GPNMB presence in the microglia in AD patients brains, especially near amyloid-β plaques, although the exact role of this protein in AD is still not fully known. Furthermore, it has been observed that GPNMB may negatively influence secretion of proinflammatory cytokines form macrophages making this glycoprotein possibly protective to neuroinflammation. Thus, the purpose of our research was to measure the concentration of GPNMB in cerebrospinal fluid of AD patients and non-demented controls and compare with classical AD biomarkers. Method:The concentrations of GPNMB was measured in cerebrospinal fluid (CSF) of 17 AD patients and 17 non-demented controls using multiplexing method.Result: GPNMB concentrations were significantly higher in AD patients in comparison to non-demented controls. Moreover, increased CSF levels of GPNMB correlated positively with Tau, pTau181, age and negatively with Aβ-42, Aβ-42/Aβ-40 ratio and MMSE in the whole study group. Conclusion:Findings of our research suggest a potential role of GPNMB in pathology of AD. However, follow-up studies on larger study group are needed.