Cerebrospinal fluid biomarkers for Parkinson disease diagnosis and progression

Ann Neurol. 2011 Mar;69(3):570-80. doi: 10.1002/ana.22311. Epub 2011 Mar 11.

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 (Aβ(1-42)), 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/Aβ(1-42) 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Alzheimer Disease / cerebrospinal fluid
  • Alzheimer Disease / diagnosis
  • Amyloid beta-Peptides / cerebrospinal fluid*
  • Analysis of Variance
  • Biomarkers / cerebrospinal fluid
  • Chemokine CX3CL1 / cerebrospinal fluid*
  • Diagnosis, Differential
  • Disease Progression*
  • Humans
  • Intracellular Signaling Peptides and Proteins / cerebrospinal fluid
  • Multiple System Atrophy / cerebrospinal fluid
  • Multiple System Atrophy / diagnosis
  • Oncogene Proteins / cerebrospinal fluid
  • Parkinson Disease / cerebrospinal fluid*
  • Parkinson Disease / diagnosis
  • Peptide Fragments / cerebrospinal fluid*
  • Phosphorylation
  • Protein Deglycase DJ-1
  • ROC Curve
  • Sensitivity and Specificity
  • Severity of Illness Index
  • alpha-Synuclein / cerebrospinal fluid
  • fms-Like Tyrosine Kinase 3 / cerebrospinal fluid*
  • tau Proteins / cerebrospinal fluid*

Substances

  • Amyloid beta-Peptides
  • Biomarkers
  • Chemokine CX3CL1
  • Intracellular Signaling Peptides and Proteins
  • Oncogene Proteins
  • Peptide Fragments
  • alpha-Synuclein
  • amyloid beta-protein (1-42)
  • tau Proteins
  • FLT3 protein, human
  • fms-Like Tyrosine Kinase 3
  • PARK7 protein, human
  • Protein Deglycase DJ-1

Grant support