Cerebrospinal fluid biomarkers for Parkinson disease diagnosis and progression

Annals of Neurology - Tập 69 Số 3 - Trang 570-580 - 2011
Min Shi1, Joshua M. Bradner1, Aneeka M. Hancock1, Kathryn A. Chung2, Joseph F. Quinn2, Elaine R. Peskind3,4, Douglas Galasko5, Joseph Jankovic6, Cyrus P. Zabetian7,8, Hojoong M. Kim7,8, James B. Leverenz7,3,4, Thomas J. Montine1, Carmen Ginghină1, Un Jung Kang9, Kevin C. Cain10, Yu Wang11,1, Jan Aasly12, David Goldstein13, Jing Zhang1
1Department of Pathology, University of Washington School of Medicine, Seattle, WA
2Department of Neurology, Oregon Health and Science University, Portland, OR
3Department of Psychiatry and Behavioral Sciences, University of Washington School of Medicine, Seattle, WA
4Mental Illness Research, Education, and Clinical Center, Veterans Affairs Puget Sound Health Care System, Seattle, WA
5Department of Neurosciences, University of California at San Diego, San Diego, CA
6Parkinson's Disease Center and Movement Disorders Clinic, Department of Neurology, Baylor College of Medicine, Houston, TX
7Department of Neurology, University of Washington School of Medicine, Seattle, WA
8Geriatric Research, Education, and Clinical Center, Veterans Affairs Puget Sound Health Care System, Seattle, WA
9Department of Neurology, University of Chicago, Chicago, IL;
10Department of Biostatistics, University of Washington School of Medicine, Seattle, WA
11Department of Neurosurgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
12Department of Neurology, St. Olavs Hospital, Trondheim, Norway
13Clinical 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

Tóm tắt

AbstractObjective: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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Annals of Neurology

Tập 69 Số 3

570-580

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