Longitudinal analyses of cerebrospinal fluid α‐Synuclein in prodromal and early Parkinson's disease
2019 | journal article. A publication with affiliation to the University of Göttingen.
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Longitudinal analyses of cerebrospinal fluid α‐Synuclein in prodromal and early Parkinson's disease
Mollenhauer, B.; Caspell‐Garcia, C. J.; Coffey, C. S.; Taylor, P.; Singleton, A.; Shaw, L. M. & Trojanowski, J. Q. et al. (2019)
Movement Disorders, 34(9) pp. 1354-1364. DOI: https://doi.org/10.1002/mds.27806
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- Authors Group
- for the PPMI study
The authors list is uncomplete: - Authors
- Mollenhauer, Brit; Caspell‐Garcia, Chelsea J.; Coffey, Christopher S.; Taylor, Peggy; Singleton, Andy; Shaw, Leslie M.; Trojanowski, John Q.; Frasier, Mark; Simuni, Tanya; Galasko, Douglas; Iranzo, Alex; Oertel, Wolfgang; Siderowf, Andrew; Weintraub, Daniel; Seibyl, John; Toga, Arthur W.; Tanner, Caroline M.; Kieburtz, Karl; Chahine, Lana M.; Marek, Kenneth
- Abstract
- 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 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society
- Issue Date
- 2019
- Publisher
- John Wiley \u0026 Sons, Inc.
- Journal
- Movement Disorders
- ISSN
- 0885-3185
- eISSN
- 1531-8257
- ISSN
- 0885-3185
- eISSN
- 1531-8257
- Language
- English
- Sponsor
- AbbVie http://dx.doi.org/10.13039/100006483
Avid Radiopharmaceuticals http://dx.doi.org/10.13039/100014392
Biogen Idec http://dx.doi.org/10.13039/100006314
Bristol‐Myers Squibb http://dx.doi.org/10.13039/100002491
Covance
Eli Lilly \u0026 Co
F. Hoffman‐La Roche, Ltd
GE Healthcare http://dx.doi.org/10.13039/100006775
Genentech http://dx.doi.org/10.13039/100004328
GlaxoSmithKline http://dx.doi.org/10.13039/100004330
Lundbeck http://dx.doi.org/10.13039/501100013327
Merck http://dx.doi.org/10.13039/100004334
MesoScale
Michael J. Fox Foundation for Parkinson's Research http://dx.doi.org/10.13039/100000864
Pfizer http://dx.doi.org/10.13039/100004319
Piramal
UCB http://dx.doi.org/10.13039/100011110