Cerebrospinal fluid biomarkers for Parkinson disease diagnosis and progression

Authors

  • Min Shi PhD,

    1. Department of Pathology, University of Washington School of Medicine, Seattle, WA
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  • Joshua Bradner MS,

    1. Department of Pathology, University of Washington School of Medicine, Seattle, WA
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  • Aneeka M. Hancock BS,

    1. Department of Pathology, University of Washington School of Medicine, Seattle, WA
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  • Kathryn A. Chung MD,

    1. Department of Neurology, Oregon Health and Science University, Portland, OR
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  • Joseph F. Quinn MD,

    1. Department of Neurology, Oregon Health and Science University, Portland, OR
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  • Elaine R. Peskind MD,

    1. Department of Psychiatry and Behavioral Sciences, University of Washington School of Medicine, Seattle, WA
    2. Mental Illness Research, Education, and Clinical Center, Veterans Affairs Puget Sound Health Care System, Seattle, WA
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  • Douglas Galasko MD,

    1. Department of Neurosciences, University of California at San Diego, San Diego, CA
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  • Joseph Jankovic MD,

    1. Parkinson's Disease Center and Movement Disorders Clinic, Department of Neurology, Baylor College of Medicine, Houston, TX
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  • Cyrus P. Zabetian MD,

    1. Geriatric Research, Education, and Clinical Center, Veterans Affairs Puget Sound Health Care System, Seattle, WA
    2. Department of Neurology, University of Washington School of Medicine, Seattle, WA
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  • Hojoong M. Kim MD,

    1. Geriatric Research, Education, and Clinical Center, Veterans Affairs Puget Sound Health Care System, Seattle, WA
    2. Department of Neurology, University of Washington School of Medicine, Seattle, WA
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  • James B. Leverenz MD,

    1. Department of Psychiatry and Behavioral Sciences, University of Washington School of Medicine, Seattle, WA
    2. Mental Illness Research, Education, and Clinical Center, Veterans Affairs Puget Sound Health Care System, Seattle, WA
    3. Department of Neurology, University of Washington School of Medicine, Seattle, WA
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  • Thomas J. Montine MD, PhD,

    1. Department of Pathology, University of Washington School of Medicine, Seattle, WA
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  • Carmen Ginghina MD,

    1. Department of Pathology, University of Washington School of Medicine, Seattle, WA
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  • Un Jung Kang MD,

    1. Department of Neurology, University of Chicago, Chicago, IL
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  • Kevin C. Cain PhD,

    1. Department of Biostatistics, University of Washington School of Medicine, Seattle, WA
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  • Yu Wang MD, PhD,

    1. Department of Pathology, University of Washington School of Medicine, Seattle, WA
    2. Department of Neurosurgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
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  • Jan Aasly MD,

    1. Department of Neurology, St. Olavs Hospital, Trondheim, Norway
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  • David Goldstein MD, PhD,

    1. 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
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  • Jing Zhang MD, PhD

    Corresponding author
    1. Department of Pathology, University of Washington School of Medicine, Seattle, WA
    • Department of Pathology, University of Washington School of Medicine, HMC Box 359635, 325 9th Ave, Seattle, WA 98104
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  • This manuscript first appeared online on 28 October 2010 as an Accepted Article on onlinelibrary.wiley.com.

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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