Original Article

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Cerebrospinal fluid biomarkers for Parkinson disease diagnosis and progression†

  1. Min Shi PhD1,
  2. Joshua Bradner MS1,
  3. Aneeka M. Hancock BS1,
  4. Kathryn A. Chung MD2,
  5. Joseph F. Quinn MD2,
  6. Elaine R. Peskind MD3,4,
  7. Douglas Galasko MD5,
  8. Joseph Jankovic MD6,
  9. Cyrus P. Zabetian MD7,8,
  10. Hojoong M. Kim MD7,8,
  11. James B. Leverenz MD3,4,8,
  12. Thomas J. Montine MD, PhD1,
  13. Carmen Ginghina MD1,
  14. Un Jung Kang MD9,
  15. Kevin C. Cain PhD10,
  16. Yu Wang MD, PhD1,11,
  17. Jan Aasly MD12,
  18. David Goldstein MD, PhD13,
  19. Jing Zhang MD, PhD1,*

Article first published online: 11 MAR 2011

DOI: 10.1002/ana.22311

Issue

Annals of Neurology

Annals of Neurology

Volume 69, Issue 3, pages 570–580, March 2011

Additional Information

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

Author Information

  1. 1

    Department of Pathology, University of Washington School of Medicine, Seattle, WA

  2. 2

    Department of Neurology, Oregon Health and Science University, Portland, OR

  3. 3

    Department of Psychiatry and Behavioral Sciences, University of Washington School of Medicine, Seattle, WA

  4. 4

    Mental Illness Research, Education, and Clinical Center, Veterans Affairs Puget Sound Health Care System, Seattle, WA

  5. 5

    Department of Neurosciences, University of California at San Diego, San Diego, CA

  6. 6

    Parkinson's Disease Center and Movement Disorders Clinic, Department of Neurology, Baylor College of Medicine, Houston, TX

  7. 7

    Geriatric Research, Education, and Clinical Center, Veterans Affairs Puget Sound Health Care System, Seattle, WA

  8. 8

    Department of Neurology, University of Washington School of Medicine, Seattle, WA

  9. 9

    Department of Neurology, University of Chicago, Chicago, IL

  10. 10

    Department of Biostatistics, University of Washington School of Medicine, Seattle, WA

  11. 11

    Department of Neurosurgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China

  12. 12

    Department of Neurology, St. Olavs Hospital, Trondheim, Norway

  13. 13

    Clinical Neurocardiology Section, Community Networks Program (CNP), Division of Intramural Research (DIR), National Institute for Neurological Disorders and Stroke (NINDS), National Institutes of Health (NIH), Bethesda, MD

*Department of Pathology, University of Washington School of Medicine, HMC Box 359635, 325 9th Ave, Seattle, WA 98104

  1. †

    This manuscript first appeared online on 28 October 2010 as an Accepted Article on onlinelibrary.wiley.com.

Publication History

  1. Issue published online: 28 MAR 2011
  2. Article first published online: 11 MAR 2011
  3. Accepted manuscript online: 28 OCT 2010 07:27AM EST
  4. Manuscript Accepted: 15 OCT 2010
  5. Manuscript Revised: 6 OCT 2010
  6. Manuscript Received: 1 JUL 2010

Funded by

  • NIH. Grant Number: ES004696
  • NIEHS. Grant Numbers: NS057567, NS060252, NS062684
  • NINDS. Grant Numbers: AG025327, AG033398, AG005136, AG008017
  • NIA. Grant Number: UL1RR025014
  • NCRR
  • 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

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Abstract

Objective:

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.

Methods:

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.

Results:

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.

Interpretation:

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

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