While diagnostic criteria have been established and validated for most neurodegenerative diseases, the considerable overlap between individual nosological entities remains a significant diagnostic challenge. Increasing evidence suggests that neurodegeneration is often initiated by inflammation within the central nervous system. The identification of inflammation could serve as a first signal of the pathophysiological process. As such, validated biological markers ("biomarkers") of neuroinflammation are critically important. This study aimed to assess the presence and levels of inflammatory biomarkers in three neurodegenerative diseases: Lewy body diseases (LBD), multiple system atrophy (MSA), and 4-repeat tauopathies (4RT). A total of 83 LBD, 24 MSA, and 31 4RT patients were included, with 83 control subjects for comparison. Six immune-related proteins were analysed in cerebrospinal fluid (CSF) and blood serum (serum): C3 complement, C4 complement, haptoglobin, transferrin, orosomucoid, and β2 microglobulin (β2M). ANCOVA statistical analysis revealed significantly lower levels of several inflammatory biomarkers in LBD (CSF: transferrin, C3 complement, orosomucoid; Serum: orosomucoid, β2M) and MSA (CSF: transferrin, C3 complement, C4 complement, orosomucoid) compared to controls. Significant differences were also observed between the synucleinopathy patient groups (LBD and MSA) and 4RT in serum levels of C3 complement. Additionally, the CSF/serum quotients for transferrin (LBD and MSA) and C3 complement (LBD) were significantly lower in disease relative to controls. These findings suggest that inflammatory processes may play a role in the pathophysiology of neurodegenerative proteinopathies, warranting further research to confirm these associations. The identification of potential fluid biomarkers would then represent a promising step forward in the field.

• Keywords
• 4-repeat tauopathies, Alpha-synucleinopathies, Biomarkers, Neurodegenerative diseases, Neuroinflammation, Parkinsonism,
• MeSH
• Biomarkers blood   cerebrospinal fluid   MeSH
• Lewy Body Disease * blood   cerebrospinal fluid   MeSH
• Middle Aged MeSH
• Humans MeSH
• Multiple System Atrophy * blood   cerebrospinal fluid   MeSH
• Neuroinflammatory Diseases * blood   cerebrospinal fluid   MeSH
• Aged MeSH
• Case-Control Studies MeSH
• Tauopathies * blood   cerebrospinal fluid   MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Comparative Study MeSH
• Names of Substances
• Biomarkers MeSH

To determine whether systemic medical factors, such as vascular risk factors, metabolic and inflammatory markers contribute to cognitive decline in Parkinson's disease (PD); if confirmed to determine whether a clinically applicable risk factor model can predict the conversion from normal cognition (NC) to mild cognitive impairment (MCI). 58 patients who met the UK Brain Bank Criteria for PD underwent clinical and laboratory assessment at study entry; 47 patients were re-assessed after 2 years. Medical history, vascular risk (QRISK2), blood metabolic and inflammatory factors, brain vessel examinations, activity of daily living, and neuropsychological testing were performed. Forty patients had NC and 18 patients had MCI at baseline. Patients with MCI had higher level of interleukin 6, folic acid below normal range and higher L-dopa equivalent dose compared to cognitive normal patients at baseline. Patients with NC at baseline were classified into two groups: patients who remained cognitively normal (non-converters, n = 23) and patients who progressed to MCI (converters, n = 11). MCI converters were older at baseline and had higher QRISK2 than the non-converters. Patients with higher QRISK2, lower uric acid level and lower activity of daily living scale at baseline had a higher risk of converting from NC to MCI with a sensitivity of 72.2%, a specificity of 87%, and an overall accuracy of 82.4%. Systemic medical factors are associated with cognitive impairment in PD both cross-sectionally and longitudinally. A risk factor model predicting the decline from NC to MCI could be constructed.

• Keywords
• Cognitive impairment, Inflammation, Metabolic factors, Parkinson’s disease, Vascular risk factors,
• MeSH
• Cerebrovascular Disorders diagnosis   epidemiology   metabolism   MeSH
• Cognitive Dysfunction diagnosis   epidemiology   metabolism   MeSH
• Cohort Studies MeSH
• Middle Aged MeSH
• Humans MeSH
• Longitudinal Studies MeSH
• Inflammation Mediators metabolism   MeSH
• Metabolic Diseases diagnosis   epidemiology   metabolism   MeSH
• Follow-Up Studies MeSH
• Parkinson Disease diagnosis   epidemiology   metabolism   MeSH
• Risk Factors MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Inflammation Mediators MeSH

The objective of this study is to assess whether elevation of serum inflammatory markers levels may indicate the progression of clinical impairment in Parkinson's disease (PD) patients. In 47 PD patients, the serum levels of the C3 and C4 part of the complement and Interleukin-6 (IL-6) were measured. The results at baseline and after 2 years were correlated with scales measuring memory, depression, motor symptoms, and quality of life. Patients with higher levels of C3 and C4 at baseline had decreased quality of life, verbal ability, and memory. Patients with higher IL-6 at baseline showed worse depression scores at 2 years. Patients with persistently higher levels of C3 and C4 at 2 years had worse quality of life and memory ability. Uncorrected p values are reported due to the exploratory nature of the study. The results indicate an impact of inflammation on non-motor signs and quality of life in PD. The increase of levels of serum inflammatory biomarkers may indicate the progression of non-motor impairment in PD.

• Keywords
• Complement, Interleukin 6, Parkinson’s disease,
• MeSH
• Biomarkers blood   MeSH
• Interleukin-6 blood   MeSH
• Complement C4 analysis   MeSH
• Complement C3 analysis   MeSH
• Middle Aged MeSH
• Humans MeSH
• Longitudinal Studies MeSH
• Parkinson Disease blood   immunology   MeSH
• Aged MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Biomarkers MeSH
• IL6 protein, human MeSH Browser
• Interleukin-6 MeSH
• Complement C4 MeSH
• Complement C3 MeSH

Objectives. The association between abnormal serum immunomarkers and mortality in 53 consecutive Parkinson's disease patients was studied. Materials and Methods. The plasma level of specific inflammatory cytokines was investigated: mannan-binding lectin (MBL), interleukin- (IL-) 6, and tumor necrosis factor-alpha (TNF-α). The baseline serum immunomarkers obtained from patients who died (n = 16) during a four-year follow-up period were compared with the data of patients who survived (n = 37). Results. The baseline level of IL-6 was significantly higher in the deceased patients than in the survivors. Elevated IL-6 levels and age were major independent contributors to disease mortality. Differences between other plasma cytokine level abnormalities were not significant. Conclusion. This study showed that IL-6 elevation may be a marker of increased mortality risk in Parkinson's disease patients. The inflammation may act in association with other factors and comorbidities in progressive neurodegenerative pathology.

• Publication type
• Journal Article MeSH