Journal article
Longitudinal analyses of cerebrospinal fluid α‐Synuclein in prodromal and early Parkinson's disease
Movement disorders, Vol.34(9), pp.1354-1364
09/2019
DOI: 10.1002/mds.27806
PMCID: PMC7098385
PMID: 31361367
Abstract
Background
Aggregation of α‐synuclein is central to the pathophysiology of PD. Biomarkers related to α‐synuclein may be informative for PD diagnosis/progression.
Objectives
To analyze α‐synuclein in CSF in drug‐naïve PD, healthy controls, and prodromal PD in the Parkinson's Progression Markers Initiative.
Methods
Over up to 36‐month follow‐up, CSF total α‐synuclein and its association with MDS‐UPDRS motor scores, cognitive assessments, and dopamine transporter imaging were assessed.
Results
The inception cohort included PD (n = 376; age [mean {standard deviation} years]: 61.7 [9.62]), healthy controls (n = 173; age, 60.9 [11.3]), hyposmics (n = 16; age, 68.3 [6.15]), and idiopathic rapid eye movement sleep behavior disorder (n = 32; age, 69.3 [4.83]). Baseline CSF α‐synuclein was lower in manifest and prodromal PD versus healthy controls. Longitudinal α‐synuclein decreased significantly in PD at 24 and 36 months, did not change in prodromal PD over 12 months, and trended toward an increase in healthy controls. The decrease in PD was not shown when CSF samples with high hemoglobin concentration were removed from the analysis. CSF α‐synuclein changes did not correlate with longitudinal MDS‐UPDRS motor scores or dopamine transporter scan.
Conclusions
CSF α‐synuclein decreases early in the disease, preceding motor PD. CSF α‐synuclein does not correlate with progression and therefore does not reflect ongoing dopaminergic neurodegeneration. Decreased CSF α‐synuclein may be an indirect index of changes in the balance between α‐synuclein secretion, solubility, or aggregation in the brain, reflecting its overall turnover. Additional biomarkers more directly related to α‐synuclein pathophysiology and disease progression and other markers to be identified by, for example, proteomics and metabolomics are needed. © 2019 International Parkinson and Movement Disorder Society
Details
- Title: Subtitle
- Longitudinal analyses of cerebrospinal fluid α‐Synuclein in prodromal and early Parkinson's disease
- Creators
- Brit Mollenhauer - University Medical Center Goettingen, Göttingen, Germany; and Paracelsus‐Elena KlinikChelsea J Caspell‐Garcia - University of IowaChristopher S Coffey - University of IowaPeggy Taylor - BioLegend IncAndy Singleton - National Institute on Aging, National Institutes of HealthLeslie M Shaw - Perelman School of Medicine, University of PennsylvaniaJohn Q Trojanowski - Perelman School of Medicine, University of PennsylvaniaMark Frasier - The Michael J. Fox Foundation for Parkinson's ResearchTanya Simuni - Northwestern University Feinberg School of MedicineAlex Iranzo - Hospital Clinic de BarcelonaWolfgang Oertel - Philipps University MarburgAndrew Siderowf - University of PennsylvaniaDaniel Weintraub - University of PennsylvaniaJohn Seibyl - Institute for Neurodegenerative DisordersArthur W Toga - Laboratory of Neuro ImagingCaroline M Tanner - University of California San FranciscoKarl Kieburtz - University of Rochester Medical CenterLana M Chahine - University of PittsburghKenneth Marek - Institute for Neurodegenerative DisordersDouglas Galasko - University of CaliforniaPPMI Study
- Resource Type
- Journal article
- Publication Details
- Movement disorders, Vol.34(9), pp.1354-1364
- DOI
- 10.1002/mds.27806
- PMID
- 31361367
- PMCID
- PMC7098385
- NLM abbreviation
- Mov Disord
- ISSN
- 0885-3185
- eISSN
- 1531-8257
- Publisher
- John Wiley & Sons, Inc
- Number of pages
- 11
- Grant note
- Avid Radiopharmaceuticals Pfizer Bristol‐Myers Squibb Genentech Biogen Idec Michael J. Fox Foundation for Parkinson's Research AbbVie Piramal UCB GE Healthcare GlaxoSmithKline F. Hoffman‐La Roche, Ltd MesoScale Eli Lilly & Co Covance Lundbeck Merck
- Language
- English
- Date published
- 09/2019
- Academic Unit
- Biostatistics
- Record Identifier
- 9984214819102771
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