This manuscript first appeared online on 28 October 2010 as an Accepted Article on onlinelibrary.wiley.com.
Cerebrospinal fluid biomarkers for Parkinson disease diagnosis and progression†
Article first published online: 11 MAR 2011
Copyright © 2011 American Neurological Association
Annals of Neurology
Volume 69, Issue 3, pages 570–580, March 2011
How to Cite
Shi, M., Bradner, J., Hancock, A. M., Chung, K. A., Quinn, J. F., Peskind, E. R., Galasko, D., Jankovic, J., Zabetian, C. P., Kim, H. M., Leverenz, J. B., Montine, T. J., Ginghina, C., Kang, U. J., Cain, K. C., Wang, Y., Aasly, J., Goldstein, D. and Zhang, J. (2011), Cerebrospinal fluid biomarkers for Parkinson disease diagnosis and progression. Ann Neurol., 69: 570–580. doi: 10.1002/ana.22311
- Issue published online: 28 MAR 2011
- Article first published online: 11 MAR 2011
- Accepted manuscript online: 28 OCT 2010 07:27AM EST
- Manuscript Accepted: 15 OCT 2010
- Manuscript Revised: 6 OCT 2010
- Manuscript Received: 1 JUL 2010
- NIH. Grant Number: ES004696
- NIEHS. Grant Numbers: NS057567, NS060252, NS062684
- NINDS. Grant Numbers: AG025327, AG033398, AG005136, AG008017
- NIA. Grant Number: UL1RR025014
- Dana Foundation
- Parkinson's Disease Foundation
- Michael J. Fox Foundation
- Friends of Alzheimer's Research
- Alzheimer's Association of Western and Central Washington
- Department of Veterans Affairs
There is a clear need to develop biomarkers for Parkinson disease (PD) diagnosis, differential diagnosis of Parkinsonian disorders, and monitoring disease progression. We and others have demonstrated that a decrease in DJ-1 and/or α-synuclein in the cerebrospinal fluid (CSF) is a potential index for Parkinson disease diagnosis, but not for PD severity.
Using highly sensitive and quantitative Luminex assays, we measured total tau, phosphorylated tau, amyloid beta peptide 1–42 (Aβ1–42), Flt3 ligand, and fractalkine levels in CSF in a large cohort of PD patients at different stages as well as healthy and diseased controls. The utility of these 5 markers was evaluated for disease diagnosis and severity/progression correlation alone, as well as in combination with DJ-1 and α-synuclein. The major results were further validated in an independent cohort of cross-sectional PD patients as well as in PD cases with CSF samples collected longitudinally.
The results demonstrated that combinations of these biomarkers could differentiate PD patients not only from normal controls but also from patients with Alzheimer disease (AD) and multiple system atrophy. Particularly, with CSF Flt3 ligand, PD could be clearly differentiated from multiple system atrophy, a disease that overlaps with PD clinically, with excellent sensitivity (99%) and specificity (95%). In addition, we identified CSF fractalkine/Aβ1–42 that positively correlated with PD severity in cross-sectional samples as well as with PD progression in longitudinal samples.
We have demonstrated that this panel of 7 CSF proteins could aid in Parkinson disease diagnosis, differential diagnosis, and correlation with disease severity and progression. ANN NEUROL 2010