Lipoprotein Metabolism and Bacterial Lipopolysaccharide in Parkinson's Disease

Lipoprotein Lipidic Composition, Lipopolysaccharide Binding Protein, and Bacterial Endotoxin Exposure in Parkinson's Disease: A Pilot Study

Patients with Parkinson's disease (PD) present an impaired intestinal permeability with consequent lipopolysaccharide (LPS) translocation in the systemic circulation. Plasmatic lipoproteins play a key role in the detoxification of LPS.

The investigators aim to study the relationships between lipoprotein chemical composition and plasma LPS circulation in PD.

Bacterial lipopolysaccharides are able to produce neuroinflammation and dopaminergic receptors degeneration. In addition, they may produce an accumulation of α-synuclein in the area of the substantia Nigra. Recent studies have shown that α-synuclein aggregates may be present also in gastrointestinal neurons of patients with PD. This last finding led to the hypothesis that the intestine might be an early site of PD disease in response to an environmental toxin or pathogen. Forsyth et al. have discovered an impaired intestinal permeability in subjects with recently diagnosed PD, and they found positive correlations between this factor, exposure to LPS and alpha-synuclein accumulation in gastrointestinal neurons. Plasma lipoproteins play a key role in the detoxification of bacterial endotoxins. Lipoprotein chemical composition is related to their detoxing properties. To the best of investigator knowledge, the relationships between lipoprotein chemical composition and LPS in PD have not yet been investigated. Therefore, the aims of this study are: I) to evaluate the chemical composition of VLDL, LDL and HDL in subjects with PD compared to a control group; 2) to analyze the activity of plasma lipid transfer proteins and LPS plasma levels in the same groups of subjects; III) finally, to investigate the correlations between the analyzed parameters.

Subjects and method Twenty patients with PD and twenty healthy controls were recruited for the study. Fasting blood samples were taken for routine laboratory analysis and for the separation of EDTA plasma. Plasma samples stored at -80°C until were used for lipoprotein isolation and analysis and for the measurement of lipid transfer protein and LPS levels.

Parkinson's patients

Inclusion Criteria:

• Diagnosis of Parkinson disease in agreement with UK Brain Bank
• Farmacological treatment with L-Dopa and/or dopaminergic agonist or diagnosis de novo
• BMI 18.5 - 29.9 kg/m^2
• Informed consent signature

Exclusion criteria:

• Presence of type 1 and type 2 diabetes mellitus
• Presence of major chronic diseases of the digestive tract.
• Pregnancy in progress
• Subjects subjected to antihypertensive therapies or statins or with drugs that can change metabolic status and insulin sensitivity (e.g. chronic oral steroid therapy)
• Subjects affected by endocrine pathologies (e.g. Cushing disease, uncontrolled thyroid disease)
• Presence of known renal insufficiency or creatinine levels greater than 1.8 mg/dl
• Presence of chronic liver disease or ALT and AST levels exceeding two standard deviations from normal levels
• Presence of malignant disease
• Alcohol or drug abuse
• Major psychiatric disorders
• Subjects dedicated to intense and agonistic physical activity.

Control group

Inclusion criteria

• Absence of major disease
• BMI 18.5 - 29.9 kg/m^2
• Informed consent signature

Exclusion Criteria:

• Presence of type 1 and type 2 diabetes mellitus
• Presence of major chronic diseases of the digestive tract.
• Pregnancy in progress
• Subjects subjected to antihypertensive therapies or statins or with drugs that can change metabolic status and insulin sensitivity (e.g. chronic oral steroid therapy)
• Subjects affected by endocrine pathologies (e.g. Cushing disease, uncontrolled thyroid disease)
• Presence of known renal insufficiency or creatinine levels greater than 1.8 mg/dl
• Presence of chronic liver disease or ALT and AST levels exceeding two standard deviations from normal levels
• Presence of malignant disease
• Alcohol or drug abuse
• Major psychiatric disorders
• Subjects dedicated to intense and agonistic physical activity.