Biomarkers in Parkinsonian Syndromes

Parkinson disease (PD), multiple system atrophy (MSA) and progressive supranuclear palsy (PSP) are neurodegenerative disorders. PD and MSA are alpha-synucleinopathies, which are characterized by the abnormal accumulation of alpha-synuclein, while tau protein accumulates in PSP. The development of biological markers for the diagnosis and prognosis in PD, MSA and PSP remains an unmet need. Such biological markers are crucial for future disease-modification and neuroprotection trials. Alpha-synuclein has a high potential for biomarker development since it constitutes the pathological hallmark feature in PD and MSA. The oligomeric alpha-synuclein seems to be particularly involved in abnormal protein aggregation in alpha-synucleinopathies.

The main objective is to compare oligomeric alpha-synuclein CSF levels between PD, MSA and PSP patients. PD and MSA patients will receive Cerebrospinal Fluid (CSF) and blood sampling at two study visits (baseline and after 12 months). Major secondary objectives are (i) to assess potential associations between the biomarker and clinical measures of disease severity and progression in MSA and PSP, and (ii) to assess the variation of the biomarker and its correlation to disease severity and progression in PD, MSA and PSP.

The differential diagnosis between Parkinson's disease, multiple system atrophy and progressive supranuclear palsy can be very difficult in early disease. PD, MSA and PSP are neurodegenerative disorders. PD and MSA belong to the alpha-synucleinopathies, which are characterized by the abnormal accumulation of alpha-synuclein. Alpha-synuclein accumulates in intraneuronal Lewy bodies in PD patients and as intracytoplasmic glial inclusions in MSA. In PSP, tau protein accumulates in neurons and glia cells while alpha-synuclein deposits are only found to a small extend.

The development of biological markers for the diagnosis and prognosis of PD, MSA and PSP remains an unmet need. Beyond guiding clinical decision-making, such biological markers are crucial for future disease-modification and neuroprotection trials.

Alpha-synuclein has a high potential for biomarker development since it constitutes the pathological hallmark feature of PD and MSA. The oligomeric alpha-synuclein fraction whose CSF levels are increased in PD seems to be particularly involved in abnormal protein aggregation in alpha-synucleinopathies.

The main objective of the study is to compare oligomeric alpha-synuclein CSF levels between PD, MSA and PSP patients. Secondary objectives are (i) to compare total alpha-synuclein levels and the index total/oligomeric alpha-synuclein between PD, MSA and PSP, (ii) to study the correlation and concordance between CSF and plasma levels of total and oligomeric alpha-synuclein, (iii) to assess potential associations between the biomarker and clinical measures of disease severity and progression and (iv) to assess the variation of the biomarker over time and its correlation to disease severity and progression.

Eligibility Criteria:
Patients receiving anticoagulants, showing abnormal coagulation on blood testing or thrombocytopenia are excluded from this study.

Patients showing more than 500 erythrocytes per mm3 of LCR are excluded from this study.

* PD patients

  * inclusion criteria:

    * Patients suffering from PD according to clinical criteria (Hughes et al, 1992)
    * Written informed consent
    * Patient covered by the national health system
  * exclusion criteria:

    * Patient under tutelage
    * patient covered by the national health system
* MSA patients

  * inclusion criteria:

    * Patients suffering from "possible" or "probable" MSA according to clinical consensus criteria (Gilman et al, 2008), age \> 30
    * Written informed consent
    * Patient covered by the national health system
  * exclusion criteria:

    * UMSARS IV score \>4 points
    * Patient under tutelage
* PSP patients

  * inclusion criteria:

    * Patients suffering from PSP according to NNIPPS trial criteria (Bensimon et al., 2009), age \> 40
    * Written informed consent
    * Patient covered by the national health system
  * exclusion criteria:

    * PSPRS item 26 score \>3 points
    * Patient under tutelage