Parkinson's disease (PD) diagnosis is mainly based on clinical criteria, with a high risk of misdiagnosis. The identification of reliable biomarkers for disease diagnosis and progression has a key role for developing disease‐modifying therapies. In this article, we investigated the longitudinal changes of CSF α‐synuclein species in early PD patients and explored the potential use of these species as surrogate biomarkers for PD progression.
We used our newly developed enzyme‐linked immunosorbent assay systems for measuring different forms of α‐synuclein, such as oligomeric‐α‐synuclein, phosphorylated‐α‐synuclein at serine 129, or total‐α‐synuclein in CSF from the longitudinal Deprenyl and Tocopherol Antioxidative Therapy for Parkinsonism study cohort (n = 121). CSF Alzheimer's disease biomarkers (total‐tau, phosphorylated‐tau, Aβ40, and Aβ42) were also measured for this cohort.
Interestingly, total‐α‐synuclein and oligomeric‐α‐synuclein levels significantly increased during the 2‐year Deprenyl and Tocopherol Antioxidative Therapy for Parkinsonism study follow‐up period, whereas phosphorylated‐α‐synuclein at serine 129 levels showed a longitudinal decrease. We have also noted an association between a change of the oligomeric‐α‐synuclein/total‐α‐synuclein ratio and a worsening of motor signs, in particular in the postural‐instability and gait‐difficulty dominant PD group. A strong positive correlation between the changes in CSF total‐α‐synuclein and oligomeric‐α‐synuclein during the 2‐year Deprenyl and Tocopherol Antioxidative Therapy for Parkinsonism study was also noted (r = 0.84, P < .001).
Our data show that CSF α‐synuclein species have a dynamic pattern along the course of the disease, supporting their possible role as progression biomarkers for PD and their link with PD clinical phenotypes.