Cerebrospinal fluid biomarkers for Parkinson disease diagnosis and progression
- 28 October 2010
- journal article
- research article
- Published by Wiley in Annals of Neurology
- Vol. 69 (3), 570-580
- https://doi.org/10.1002/ana.22311
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 2010Keywords
This publication has 53 references indexed in Scilit:
- CSF Aβ42 and tau in Parkinson's disease with cognitive impairmentMovement Disorders, 2010
- DJ-1 and α-synuclein in human cerebrospinal fluid as biomarkers of Parkinson’s diseaseBrain, 2010
- High-resolution diffusion tensor imaging in the substantia nigra of de novo Parkinson diseaseNeurology, 2009
- Cerebrospinal fluid α-synuclein in neurodegenerative disorders—A marker of synapse loss?Neuroscience Letters, 2009
- CSF Multianalyte Profile Distinguishes Alzheimer and Parkinson DiseasesAmerican Journal of Clinical Pathology, 2008
- Validation of amyloid-β peptides in CSF diagnosis of neurodegenerative dementiasMolecular Psychiatry, 2007
- Decreased α-synuclein in cerebrospinal fluid of aged individuals and subjects with Parkinson’s diseaseBiochemical and Biophysical Research Communications, 2006
- Increased level of DJ-1 in the cerebrospinal fluids of sporadic Parkinson’s diseaseBiochemical and Biophysical Research Communications, 2006
- Regional brain volumes distinguish PSP, MSA‐P, and PD: MRI‐based clinico‐radiological correlationsMovement Disorders, 2006
- The FLT3 Tyrosine Kinase Receptor Inhibits Neural Stem/Progenitor Cell Proliferation and Collaborates with NGF to Promote Neuronal SurvivalMolecular and Cellular Neuroscience, 2001