Cerebrospinal Fluid Alpha-Synuclein Species In Cognitive And Movements Disorders

Total CSF alpha-synuclein (t-alpha-syn), phosphorylated alpha-syn (pS129-alpha-syn) and alpha-syn oligomers (o-alpha-syn) have been studied as candidate biomarkers for synucleinopathies, with suboptimal specificity and sensitivity in the differentiation from healthy controls. Studies of alpha-syn species in patients with other underlying pathologies are lacking. The aim of this study was to investigate possible alterations in CSF alpha-syn species in a cohort of patients with diverse underlying pathologies. A total of 135 patients were included, comprising Parkinson's disease (PD; n = 13), multiple system atrophy (MSA; n = 9), progressive supranuclear palsy (PSP; n = 13), corticobasal degeneration (CBD; n = 9), Alzheimer's disease (AD; n = 51), frontotemporal degeneration (FTD; n = 26) and vascular dementia patients (VD; n = 14). PD patients exhibited higher pS129-alpha-syn/alpha-syn ratios compared to FTD (p = 0.045), after exclusion of samples with CSF blood contamination. When comparing movement disorders (i.e., MSA vs. PD vs. PSP vs. CBD), MSA patients had lower alpha-syn levels compared to CBD (p = 0.024). Patients with a synucleinopathy (PD and MSA) exhibited lower t-alpha-syn levels (p = 0.002; cut-off value: <= 865 pg/mL; sensitivity: 95%, specificity: 69%) and higher pS129-/t-alpha-syn ratios (p = 0.020; cut-off value: >= 0.122; sensitivity: 71%, specificity: 77%) compared to patients with tauopathies (PSP and CBD). There are no significant alpha-syn species alterations in non-synucleinopathies.