α-Synuclein and tau concentrations in cerebrospinal fluid of patients presenting with parkinsonism: a cohort study

The Parkinson's progression markers initiative (PPMI) – establishing a PD biomarker cohort

“…There was no difference in A‐Beta levels between PD and HC subjects. Prior studies have shown similar changes in α‐syn and tau in PD subjects,29, 49, 50, 51, 52 but the PPMI cohort is unique as a large, prospectively enrolled, previously untreated PD cohort with well‐characterized clinical, imaging, biospecimen, and genetic biomarkers.…”

“…CSF α‐syn was analyzed at a central laboratory (Covance, MA, US) using a commercially available enzyme‐linked immunosorbent assay kit. This kit was developed and optimized for PPMI 29, 30. Briefly, 200  μ L/well of diluted α‐syn standards (range, 6.1–1500 pg/mL) using reconstituted stock and diluted duplicate CSF samples (200  μ L/well) were added to the capture antibody–coated plate after washing the plate four times.…”

“…The concentration of α ‐syn was measured using standard curves with four‐parameter curve fitting. Cross‐reactivity with β ‐syn or γ ‐syn has not been observed with the antibodies used in this assay 29, 30. CSF hemoglobin was measured at Covance using an enyzme‐linked immunosorbent assay method with reagents obtained from Bethyl Laboratories according to the manufacturer's instruction.…”

Novel One-step Immunoassays to Quantify α-Synuclein

“…However, among these reports there are inconsistencies in both the reported absolute concentration of CSF ␣-synuclein and the putative nature of its change in the PD condition. Indeed, although some studies found reduced CSF ␣-synuclein in PD relative to controls (15)(16)(17)(18)(19), another reported no change (20). There is further disparity in findings comparing CSF ␣-synuclein in PD and synucleinopathies to that of other neurodegenerative disorders (16, 20 -24).…”

Proteolytic clearance of extracellular α-synuclein as a new therapeutic approach against Parkinson disease

“…[8][9][10] In addition, α-syn and its aggregates have been shown to be secreted from neuronal cells by a non-classical exocytic pathway 11 and its release is increased under various protein misfolding stress conditions. 12 α-Syn has also been reported to be secreted in a calcium-dependent manner by exosomes, 13 and lysosomal dysfunction increases exosome-mediated α-syn release.…”