LiMBaLiP: Lipoprotein Metabolism and Bacterial Lipopolysaccharide in Parkinson's Disease
Study Details
Study Description
Brief Summary
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Detailed Description
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Parkinson's patients Patients with Parkinson disease evaluated in agreement with UK Brain Bank criteria |
Other: Patients not treated
|
| Control group Subject matched for sex, age and BMI |
Other: Patients not treated
|
Outcome Measures
Primary Outcome Measures
- LPS [through study completion an average of 1 year]
LPS plasma levels (EU/L)
- Lipoprotein chemical composition [through study completion an average of 1 year]
Cholesterol (mg/dL); HDL-cholesterol (mg/dL); triglycerides (mg/dL); phospholipids (mg/dL), apoproteins (mg/dL) of VLDL, LDL and HDL
Secondary Outcome Measures
- Plasma lipid transfer proteins [through study completion an average of 1 year]
Lipopolysaccharide binding protein (ng/mL), cholesterol ester transfer protein (ng/mL), phospholipid transfer protein (ng/mL)
Eligibility Criteria
Criteria
Parkinson's patients
Inclusion Criteria:
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Diagnosis of Parkinson disease in agreement with UK Brain Bank
-
Farmacological treatment with L-Dopa and/or dopaminergic agonist or diagnosis de novo
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BMI 18.5 - 29.9 kg/m^2
-
Informed consent signature
Exclusion criteria:
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Presence of type 1 and type 2 diabetes mellitus
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Presence of major chronic diseases of the digestive tract.
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Pregnancy in progress
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Subjects subjected to antihypertensive therapies or statins or with drugs that can change metabolic status and insulin sensitivity (e.g. chronic oral steroid therapy)
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Subjects affected by endocrine pathologies (e.g. Cushing disease, uncontrolled thyroid disease)
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Presence of known renal insufficiency or creatinine levels greater than 1.8 mg/dl
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Presence of chronic liver disease or ALT and AST levels exceeding two standard deviations from normal levels
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Presence of malignant disease
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Alcohol or drug abuse
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Major psychiatric disorders
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Subjects dedicated to intense and agonistic physical activity.
Control group
Inclusion criteria
-
Absence of major disease
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BMI 18.5 - 29.9 kg/m^2
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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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | ASST Centro Specialistico Ortopedico Traumatologico Gaetano Pini-CTO | Milan | Italy | 20136 |
Sponsors and Collaborators
- University of Milan
- Istituti Clinici di Perfezionamento di Milano
Investigators
- Principal Investigator: Roberta Cazzola, PhD, University of Milan
Study Documents (Full-Text)
None provided.More Information
Publications
- Forsyth CB, Shannon KM, Kordower JH, Voigt RM, Shaikh M, Jaglin JA, Estes JD, Dodiya HB, Keshavarzian A. Increased intestinal permeability correlates with sigmoid mucosa alpha-synuclein staining and endotoxin exposure markers in early Parkinson's disease. PLoS One. 2011;6(12):e28032. doi: 10.1371/journal.pone.0028032. Epub 2011 Dec 1.
- Han R. Plasma lipoproteins are important components of the immune system. Microbiol Immunol. 2010 Apr;54(4):246-53. doi: 10.1111/j.1348-0421.2010.00203.x. Review.
- Hughes AJ, Ben-Shlomo Y, Daniel SE, Lees AJ. What features improve the accuracy of clinical diagnosis in Parkinson's disease: a clinicopathologic study. 1992. Neurology. 2001 Nov;57(10 Suppl 3):S34-8.
- Lebouvier T, Chaumette T, Paillusson S, Duyckaerts C, Bruley des Varannes S, Neunlist M, Derkinderen P. The second brain and Parkinson's disease. Eur J Neurosci. 2009 Sep;30(5):735-41. doi: 10.1111/j.1460-9568.2009.06873.x. Epub 2009 Aug 27. Review.
- Levels JH, Marquart JA, Abraham PR, van den Ende AE, Molhuizen HO, van Deventer SJ, Meijers JC. Lipopolysaccharide is transferred from high-density to low-density lipoproteins by lipopolysaccharide-binding protein and phospholipid transfer protein. Infect Immun. 2005 Apr;73(4):2321-6.
- Unimi