CSF GPNMB in Parkinson's disease: A potential association with age and microglial activation

Background Recent evidence suggests a link between glycoprotein non-metastatic melanoma protein B (GPNMB) and Parkinson's disease (PD) pathogenesis. Although elevated plasma GPNMB levels associated with disease severity have been reported in PD, cerebrospinal fluid (CSF) alterations remain elusive. Objective To explore CSF GPNMB alterations and its clinical significance in PD. Methods This study enrolled 118 sporadic PD patients and 40 controls. We examined the potential associations between CSF GPNMB levels and the clinical characteristics or biomarkers of neurodegenerative pathogenesis. Results PD patients had higher CSF GPNMB levels than controls ( p = 0.0159). In the PD group, CSF GPNMB levels correlated with age (age at examination: r s = 0.2511, p = 0.0061; age at onset: r s = 0.2800, p = 0.0021) and the severity of motor and cognitive dysfunction (MDS-UPDRS III score: r s = 0.1998, p = 0.0347; Mini-Mental State Examination score: r s = −0.1922, p = 0.0370). After correcting for multiple comparisons, the correlation with age at onset remained significant. CSF GPNMB levels were also positively correlated with CSF soluble triggering receptor expressed on myeloid cells 2 (sTREM2) levels in both the PD ( r s = 0.3582, p < 0.0001) and control ( r s = 0.4743, p = 0.0023) groups. Furthermore, multiple regression analysis revealed CSF sTREM2 level as the strongest determinant of CSF GPNMB levels in the PD group (t-value = 3.49, p = 0.0007). Conclusions Elevated CSF GPNMB levels, linked with age and microglial activation, may be a valuable marker for understanding the interplay between aging, neuroinflammation, and PD pathology.