Cerebrospinal fluid biomarkers for Parkinson disease diagnosis and progression

Min Shi, Joshua Bradner, Aneeka M. Hancock, Kathryn (Kathy) Chung, Joseph Quinn, Elaine R. Peskind, Douglas Galasko, Joseph Jankovic, Cyrus P. Zabetian, Hojoong M. Kim, James B. Leverenz, Thomas J. Montine, Carmen Ginghina, Un Jung Kang, Kevin C. Cain, Yu Wang, Jan Aasly, David Goldstein, Jing Zhang

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
Pages (from-to)570-580
Number of pages11
JournalAnnals of Neurology
Volume69
Issue number3
DOIs
StatePublished - Mar 2011

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Parkinson Disease
Cerebrospinal Fluid
Disease Progression
Biomarkers
Synucleins
Chemokine CX3CL1
Multiple System Atrophy
Differential Diagnosis
Cerebrospinal Fluid Proteins
Parkinsonian Disorders
Alzheimer Disease
Sensitivity and Specificity

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

Cite this

Cerebrospinal fluid biomarkers for Parkinson disease diagnosis and progression. / Shi, Min; Bradner, Joshua; Hancock, Aneeka M.; Chung, Kathryn (Kathy); Quinn, Joseph; Peskind, Elaine R.; Galasko, Douglas; Jankovic, Joseph; Zabetian, Cyrus P.; Kim, Hojoong M.; Leverenz, James B.; Montine, Thomas J.; Ginghina, Carmen; Kang, Un Jung; Cain, Kevin C.; Wang, Yu; Aasly, Jan; Goldstein, David; Zhang, Jing.

In: Annals of Neurology, Vol. 69, No. 3, 03.2011, p. 570-580.

Research output: Contribution to journalArticle

Shi, M, Bradner, J, Hancock, AM, Chung, KK, Quinn, J, Peskind, ER, Galasko, D, Jankovic, J, Zabetian, CP, Kim, HM, Leverenz, JB, Montine, TJ, Ginghina, C, Kang, UJ, Cain, KC, Wang, Y, Aasly, J, Goldstein, D & Zhang, J 2011, 'Cerebrospinal fluid biomarkers for Parkinson disease diagnosis and progression', Annals of Neurology, vol. 69, no. 3, pp. 570-580. https://doi.org/10.1002/ana.22311
Shi, Min ; Bradner, Joshua ; Hancock, Aneeka M. ; Chung, Kathryn (Kathy) ; Quinn, Joseph ; Peskind, Elaine R. ; Galasko, Douglas ; Jankovic, Joseph ; Zabetian, Cyrus P. ; Kim, Hojoong M. ; Leverenz, James B. ; Montine, Thomas J. ; Ginghina, Carmen ; Kang, Un Jung ; Cain, Kevin C. ; Wang, Yu ; Aasly, Jan ; Goldstein, David ; Zhang, Jing. / Cerebrospinal fluid biomarkers for Parkinson disease diagnosis and progression. In: Annals of Neurology. 2011 ; Vol. 69, No. 3. pp. 570-580.
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T1 - Cerebrospinal fluid biomarkers for Parkinson disease diagnosis and progression

AU - Shi, Min

AU - Bradner, Joshua

AU - Hancock, Aneeka M.

AU - Chung, Kathryn (Kathy)

AU - Quinn, Joseph

AU - Peskind, Elaine R.

AU - Galasko, Douglas

AU - Jankovic, Joseph

AU - Zabetian, Cyrus P.

AU - Kim, Hojoong M.

AU - Leverenz, James B.

AU - Montine, Thomas J.

AU - Ginghina, Carmen

AU - Kang, Un Jung

AU - Cain, Kevin C.

AU - Wang, Yu

AU - Aasly, Jan

AU - Goldstein, David

AU - Zhang, Jing

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N2 - 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.

AB - 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.

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