Myeloperoxidase and Advanced Oxidation Protein Products in the Cerebrospinal Fluid in Women and Men with Parkinson's Disease.

Abstract

Background: Myeloperoxidase (MPO) and advanced oxidation protein products, or AOPP (a type of MPO-derived chlorinated adducts), have been implicated in Parkinson´s disease (PD). Human MPO also show sex-based differences in PD. The objective was to study the relationship of MPO and AOPP in the cerebrospinal fluid (CSF) with motor features of idiopathic PD in male and female patients. Methods: MPO concentration and activity and AOPP content were measured in the CSF and serum in 34 patients and 30 controls. CSF leukocytes and the integrity of the blood-brain barrier were evaluated. Correlations of MPO and AOPP with clinical variables were examined. Results: The blood-brain barrier was intact and CSF leukocyte count was normal in all patients. CSF MPO concentration and activity were similar in the cohort of patients and controls, but CSF MPO content was significantly higher in male patients than in PD women (p = 0.0084). CSF MPO concentration correlated with disease duration in male and female patients (pCSF MPO concentration was significantly higher in men with a disease duration ≥12 years compared to the remainder of the male subjects (p < 0.01), while changes in CSF MPO in women were not significant. Serum MPO concentration and activity were significantly higher in all PD patients relative to controls (p < 0.0001), but CSF MPO was not correlated with serum MPO. Serum AOPP were detected in all patients, but CSF AOPP was undetectable in 53% of patients, with AOPP not being quantifiable in controls. The study concluded that CSF MPO is not a good biomarker for PD because mean CSF MPO concentration and activity do not differ between the cohort of patients and controls. While CSF MPO concentration positively correlated with disease duration in both men and women, it was only significantly enhanced in male patients with a disease duration longer than 12 years. This suggests that the MPO-related immune response may be weak in early-stage PD across all patients but progressively enhanced in men, not women. Given that the blood-brain barrier is intact and CSF MPO is not correlated with serum MPO, CSF myeloperoxidase likely reflects MPO content in brain cells rather than blood-derived cells. Finally, serum AOPP was detected in all patients but not controls, indicating the occurrence of chlorinative stress in blood serum in PD. The study of CSF AOPP as a biomarker could not be assessed due to the limitations of the ELISA assay in detecting it in the CSF.