Session Information
Date: Sunday, October 7, 2018
Session Title: Other
Session Time: 1:45pm-3:15pm
Location: Hall 3FG
Objective: To examine the longitudinal relationships between total alpha-synuclein (aSyn) changes in cerebrospinal fluid (CSF), clinical measures, and factors that may influence CSF aSyn in an inception cohort of drug-naïve Parkinson’s disease (PD) patients and healthy controls (HC) and prodromal PD participants in the Parkinson’s Progression Markers Initiative (PPMI).
Background: Objective progression biomarkers are needed to support clinical trials. The 10-15% decrease in CSF aSyn in PD is a consistent finding in cross sectional studies. In a previous PPMI analysis, we reported no change in CSF biomarkers in PD and HC over 12 months despite clinical progression (1).
Methods: Longitudinal levels of CSF total aSyn were measured in 376 PD participants and 173 matched HC at baseline and 6, 12, 24 and 36 months. A prodromal cohort comprising 16 hyposmic participants and 32 with isolated REM sleep behavior disorder (iRBD) had CSF sampled at baseline, 6 and 12 months. Relationships between aSyn levels and changes in motor and cognitive assessments and dopamine transporter imaging were assessed.
Results: Baseline CSF aSyn levels were lower in PD, hyposmics and iRBD compared to HC. Levels decreased slightly but significantly in PD at 24 and 36 months, and trended towards an increase in HC. CSF aSyn changes did not correlate with changes in MDS-UPDRS motor scores or dopamine transporter imaging. While baseline CSF aSyn levels in iRBD were lower than in HC, levels in hyposmic participants were even lower than in PD. In both prodromal cohorts, aSyn levels did not change over 12 months.
Conclusions: CSF aSyn remained stable in all groups over 12 months, but decreased significantly over 36 months in PD. This small change did not correlate with clinical progression and is therefore probably not very meaningful. Therefore novel biomarkers are needed that reflect the earlier neurodegenerative process and clinical progression.
References: (1) Mollenhauer B, Caspell-Garcia CJ, Coffey CS, et al. Longitudinal CSF biomarkers in patients with early Parkinson disease and healthy controls. Neurology. Nov 7 2017;89(19):1959-1969.
To cite this abstract in AMA style:
B. Mollenhauer, C. Caspell-Garcia, C. Coffey, P. Taylor, A. Singleton, L. Shaw, J. Trojanowski, M. Frasier, T. Simuni, A. Siderowf, K. Marek, D. Galasko. Longitudinal alpha-synuclein in cerebrospinal fluid in early Parkinson’s disease, prodromal PD and healthy controls [abstract]. Mov Disord. 2018; 33 (suppl 2). https://www.mdsabstracts.org/abstract/longitudinal-alpha-synuclein-in-cerebrospinal-fluid-in-early-parkinsons-disease-prodromal-pd-and-healthy-controls/. Accessed June 15, 2025.« Back to 2018 International Congress
MDS Abstracts - https://www.mdsabstracts.org/abstract/longitudinal-alpha-synuclein-in-cerebrospinal-fluid-in-early-parkinsons-disease-prodromal-pd-and-healthy-controls/