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: rs = 0.2511, p = 0.0061; age at onset: rs = 0.2800, p = 0.0021) and the severity of motor and cognitive dysfunction (MDS-UPDRS III score: rs = 0.1998, p = 0.0347; Mini-Mental State Examination score: rs = -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 (rs = 0.3582, p < 0.0001) and control (rs = 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.