Longitudinal changes in CSF alpha-synuclein species reflect Parkinson's disease progression.

Abstract

BACKGROUND:

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.

METHODS:

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.

RESULTS:

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).

CONCLUSION:

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. © 2016 International Parkinson and Movement Disorder Society.

• Authors: Nour K Majbour, Nishant N Vaikath, Paolo Eusebi, Davide Chiasserini, Mustafa Ardah, Shiji Varghese, M Emdadul Haque, Takahiko Tokuda, Peggy Auinger, Paolo Calabresi, Lucilla Parnetti, Omar M A El-Agnaf
• Journal: Movement disorders : official journal of the Movement Disorder Society (Mov Disord) Vol. 31 Issue 10 Pg. 1535-1542 (10 2016) ISSN: 1531-8257 [Electronic] United States
• PMID: 27548849 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2016 International Parkinson and Movement Disorder Society.

Chemical References

• Antioxidants
• Biomarkers
• alpha-Synuclein

Topics

• Aged
• Antioxidants (therapeutic use)
• Biomarkers (cerebrospinal fluid)
• Disease Progression
• Female
• Humans
• Longitudinal Studies
• Male
• Middle Aged
• Parkinson Disease (cerebrospinal fluid, drug therapy)
• alpha-Synuclein (cerebrospinal fluid)