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CSF GPNMB in Parkinson's disease: A potential association with age and microglial activation
Xi-Chen Zhu1,2, Yasuaki Mizutani1, Reiko Ohdake1
1Department of Neurology, Fujita Health University School of Medicine, Toyoake, Aichi, Japan.
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.
Insights
Cerebrospinal fluid (CSF) glycoprotein non-metastatic melanoma protein B (GPNMB) levels are elevated in Parkinson's disease (PD) patients and correlate with age and disease severity. This suggests GPNMB may be a marker for neuroinflammation in PD.
Area of Science:
- Neuroscience
- Biochemistry
- Pathology
Background:
- Glycoprotein non-metastatic melanoma protein B (GPNMB) is implicated in Parkinson's disease (PD) pathogenesis.
- While elevated plasma GPNMB is noted in PD, its role in cerebrospinal fluid (CSF) is unclear.
Purpose of the Study:
- To investigate alterations in CSF GPNMB levels in PD patients.
- To determine the clinical significance of CSF GPNMB in relation to disease characteristics and biomarkers.
Main Methods:
- CSF GPNMB levels were measured in 118 PD patients and 40 controls.
- Associations between CSF GPNMB and clinical data (age, motor/cognitive scores) and CSF sTREM2 were analyzed.
Main Results:
- PD patients exhibited significantly higher CSF GPNMB levels compared to controls.
- CSF GPNMB correlated with age of onset, motor severity (MDS-UPDRS III), and cognitive function (MMSE).
- CSF GPNMB levels were positively associated with CSF sTREM2, a marker of microglial activation, in both PD and control groups.
Conclusions:
- Elevated CSF GPNMB in PD is linked to aging and neuroinflammation.
- CSF GPNMB may serve as a biomarker for understanding the complex interplay of aging, neuroinflammation, and PD pathology.
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