Development of Biomarkers for the Diagnosis and Prognosis of Parkinsonian Syndromes Running Head: Biomarkers in Parkinsonian Syndromes

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.