Format

Send to

Choose Destination
Mov Disord. 2019 Sep;34(9):1354-1364. doi: 10.1002/mds.27806. Epub 2019 Jul 30.

Longitudinal analyses of cerebrospinal fluid α-Synuclein in prodromal and early Parkinson's disease.

Author information

1
Department of Neurology, University Medical Center Goettingen, Göttingen, Germany; and Paracelsus-Elena Klinik, Kassel, Germany.
2
Department of Biostatistics, College of Public Health, University of Iowa, Iowa City, Iowa, USA.
3
BioLegend Inc., San Diego, California, USA.
4
Molecular Genetics Section, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, Maryland, USA.
5
Department of Pathology & Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
6
Center for Neurodegenerative Disease Research, Institute on Aging, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
7
Morris K. Udall Center of Excellence for Parkinson's Disease Research, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
8
The Michael J. Fox Foundation for Parkinson's Research, New York, New York, USA.
9
Parkinson's Disease and Movement Disorders Center, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
10
Neurological Service, Hospital Clinic de Barcelona, Barcelona, Spain.
11
Department of Neurology, Philipps University Marburg, Marburg, Germany.
12
Department of Neurology Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
13
Institute for Neurodegenerative Disorders, New Haven, Connecticut, USA.
14
University of Southern California, Laboratory of Neuro Imaging, Los Angeles, California, USA.
15
Department of Neurology, University of California San Francisco, San Francisco, California, USA.
16
Clinical Trials Coordination Center, University of Rochester Medical Center, Rochester, New York, USA.
17
Department of Neurology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
18
Department of Neurosciences, University of California, San Diego, San Diego, California, USA.

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.

KEYWORDS:

Parkinson's disease/parkinsonism; cohort studies; outcome research

PMID:
31361367
DOI:
10.1002/mds.27806

Supplemental Content

Full text links

Icon for Wiley
Loading ...
Support Center