Tau/α-synuclein ratio and inflammatory proteins in Parkinson's disease: An exploratory study

Mov Disord. 2017 Jul;32(7):1066-1073. doi: 10.1002/mds.27001. Epub 2017 May 26.

Abstract

Background: No CSF or plasma biomarker has been validated for diagnosis or progression of PD.

Objectives: To assess whether the CSF and plasma levels of proteins associated with PD neuropathological inclusions and with neuroinflammation might have value in the diagnosis of PD or in relation to disease severity.

Methods: CSF levels of α-synuclein, amyloid-ß1-42, total tau, and threonine-181 phosphorylated tau, as well as CSF and plasma levels of cytokines (interleukin-1ß, interleukin-2, interleukin, interferon-γ, and tumor necrosis factor α) were studied in 40 PD patients and 40 healthy controls. Plasma levels of cytokines were measured in 51 patients and 26 aditional controls. We also explored the Parkinson's Progression Markers Initiative data set as a replication cohort.

Results: CSF levels of α-synuclein, amyloid-ß1-42, and tumor necrosis factor α were lower in patients than in controls, and the total tau/α-synuclein, phosphorylated tau/α-synuclein, total tau/amyloid-ß1-42+α-synuclein, and phosphorylated tau/amyloid-ß1-42+α-synuclein ratios were higher in patients. The best area under the curve value was obtained for the phosphorylated tau/α-synuclein ratio alone (0.86) and also when this was combined with tumor necrosis factor α in CSF (0.91; sensitivity 92.9%, specificity 75% for a cut-off value of ≤ 0.71). Phosphorylated tau/α-synuclein and phosphorylated tau/amyloid-ß1-42+α-synuclein were higher in patients than in controls of the Parkinson's Progression Markers Initiative database. Plasma cytokines did not differ between groups, although interleukin-6 levels were positively correlated with UPDRS-I, -II, and -III scores.

Conclusions: The CSF phosphorylated tau/α-synuclein ratio alone, and in combination with tumor necrosis factor α and plasma interleukin-6 levels, might serve as biomarkers to diagnose PD and monitor its severity. © 2017 International Parkinson and Movement Disorder Society.

Keywords: IL-6; Parkinson's disease; biomarkers; cerebrospinal fluid; α-synuclein.

MeSH terms

  • Aged
  • Amyloid beta-Peptides / cerebrospinal fluid*
  • Biomarkers / blood
  • Biomarkers / cerebrospinal fluid
  • Disease Progression
  • Female
  • Humans
  • Interferon-gamma / blood
  • Interferon-gamma / cerebrospinal fluid
  • Interleukin-1beta / blood
  • Interleukin-1beta / cerebrospinal fluid
  • Interleukin-2 / blood
  • Interleukin-2 / cerebrospinal fluid
  • Interleukin-6 / blood*
  • Interleukin-6 / cerebrospinal fluid
  • Male
  • Middle Aged
  • Parkinson Disease / blood*
  • Parkinson Disease / cerebrospinal fluid*
  • Parkinson Disease / physiopathology
  • Peptide Fragments / cerebrospinal fluid*
  • Severity of Illness Index*
  • Tumor Necrosis Factor-alpha / blood
  • Tumor Necrosis Factor-alpha / cerebrospinal fluid*
  • alpha-Synuclein / cerebrospinal fluid*
  • tau Proteins / cerebrospinal fluid*

Substances

  • Amyloid beta-Peptides
  • Biomarkers
  • IL1B protein, human
  • IL2 protein, human
  • IL6 protein, human
  • Interleukin-1beta
  • Interleukin-2
  • Interleukin-6
  • Peptide Fragments
  • TNF protein, human
  • Tumor Necrosis Factor-alpha
  • alpha-Synuclein
  • amyloid beta-protein (1-42)
  • tau Proteins
  • Interferon-gamma