Sortilin Expression Levels and Peripheral Immunity: A Potential Biomarker for Segregation between Parkinson's Disease Patients and Healthy Controls.

Parkinson's disease (PD) is characterized by substantial phenotypic heterogeneity that limits the disease prognosis and patient's counseling, and complicates the design of further clinical trials. There is an unmet need for the development and validation of biomarkers for the prediction of the disease course. In this study, we utilized flow cytometry and in vitro approaches on peripheral blood cells and isolated peripheral blood mononuclear cell (PBMC)-derived macrophages to characterize specific innate immune populations in PD patients versus healthy donors. We found a significantly lower percentage of B lymphocytes and monocyte populations in PD patients. Monocytes in PD patients were characterized by a higher CD40 expression and on-surface expression of the type I membrane glycoprotein sortilin, which showed a trend of negative correlation with the age of the patients. These results were further investigated in vitro on PBMC-derived macrophages, which, in PD patients, showed higher sortilin expression levels compared to cells from healthy donors. The treatment of PD-derived macrophages with oxLDL led to higher foam cell formation compared to healthy donors. In conclusion, our results support the hypothesis that surface sortilin expression levels on human peripheral monocytes may potentially be utilized as a marker of Parkinson's disease and may segregate the sporadic versus the genetically induced forms of the disease.

Parkinson's Disease, It Takes Guts: The Correlation between Intestinal Microbiome and Cytokine Network with Neurodegeneration.

Parkinson's disease is a progressive neurodegenerative disorder with motor, physical and behavioral symptoms that can have a profound impact on the patient's quality of life. Most cases are idiopathic, and the exact mechanism of the disease's cause is unknown. The current hypothesis focuses on the gut-brain axis and states that gut microbiota dysbiosis can trigger inflammation and advances the development of Parkinson's disease. This systematic review presents the current knowledge of gut microbiota analysis and inflammation based on selected studies on Parkinson's patients and experimental animal models. Changes in gut microbiota correlate with Parkinson's disease, but only a few studies have considered inflammatory modulators as important triggers of the disease. Nevertheless, it is evident that proinflammatory cytokines and chemokines are induced in the gut, the circulation, and the brain before the development of the disease's neurological symptoms and exacerbate the disease. Increased levels of tumor necrosis factor, interleukin-1ß, interleukin-6, interleukin-17A and interferon-γ can correlate with altered gut microbiota. Instead, treatment of gut dysbiosis is accompanied by reduced levels of inflammatory mediators in specific tissues, such as the colon, brain and serum and/or cerebrospinal fluid. Deciphering the role of the immune responses and the mechanisms of the PD-associated gut microbiota will assist the interpretation of the pathogenesis of Parkinson's and will elucidate appropriate therapeutic strategies.

Peripheral Inflammatory Markers TNF-α and CCL2 Revisited: Association with Parkinson's Disease Severity.

One of the major mediators of neuroinflammation in PD is tumour necrosis factor alpha (TNF-α), which, similar to other cytokines, is produced by activated microglia and astrocytes. Although TNF-α can be neuroprotective in the brain, long-term neuroinflammation and TNF release can be harmful, having a neurotoxic role that leads to death of oligodendrocytes, astrocytes, and neurons and, therefore, is associated with neurodegeneration. Apart from cytokines, a wide family of molecules with homologous structures, namely chemokines, play a key role in neuro-inflammation by drawing cytotoxic T-lymphocytes and activating microglia. The objective of the current study was to examine the levels of the serum TNF-α and CCL2 (Chemokine (C-C motif) ligand 2), also known as MCP-1 (Monocyte Chemoattractant Protein-1), in PD patients compared with healthy controls. We also investigated the associations between the serum levels of these two inflammatory mediators and a number of clinical symptoms, in particular, disease severity and cognition. Such an assessment may point to their prognostic value and provide some treatment hints. PD patients with advanced stage on the Hoehn-Yahr scale showed an increase in TNF-α levels compared with PD patients with stages 1 and 2 (p = 0.01). Additionally, the UPDRS score was significantly associated with TNF-α levels. CCL2 levels, however, showed no significant associations.