Soluble CD163 Changes Indicate Monocyte Association With Cognitive Deficits in Parkinson's Disease

Area of Science:

• Neuroimmunology
• Neurodegenerative Diseases
• Biomarker Discovery

Background:

• Parkinson's disease (PD) involves immune system changes, but specific cell contributions are unclear.
• Immune biomarkers in PD patients' biofluids are altered, yet their cellular origins remain largely unknown.
• Identifying specific immune cells involved in PD pathogenesis is crucial for understanding disease mechanisms.

Purpose of the Study:

• To investigate the role of monocytes in Parkinson's disease.
• To explore the monocyte-specific biomarker sCD163 in PD patients' cerebrospinal fluid (CSF) and serum.
• To examine potential links between CD163 and alpha-synuclein in vitro.

Main Methods:

• Measured sCD163 levels in CSF and serum from PD patients.
• Compared sCD163 with other PD biomarkers and clinical/cognitive data.
• Investigated in vitro interactions between alpha-synuclein and CD163 in myeloid cells.

Main Results:

• CSF-sCD163 increased in late-stage PD, correlating with PD biomarkers and inversely with cognitive scores.
• Serum-sCD163 elevation was observed only in female PD patients, indicating sex-specific immune responses.
• CSF-sCD163 correlated with immune activation markers, while serum-sCD163 linked to systemic inflammation.
• In vitro, alpha-synuclein induced sCD163 shedding, enhancing its own uptake by myeloid cells.

Conclusions:

• sCD163 shows potential as a cognition-related biomarker in PD.
• Monocytes are implicated in both peripheral and central immune responses in PD.
• Alpha-synuclein's inflammatory properties may influence monocyte activity and PD progression.