GDF15/MIC1 and MMP9 Cerebrospinal Fluid Levels in Parkinson's Disease and Lewy Body Dementia

PLoS One. 2016 Mar 3;11(3):e0149349. doi: 10.1371/journal.pone.0149349. eCollection 2016.

Abstract

Based on animal and ex-vivo experiments, Growth/Differentiation Factor-15 (GDF15, also called Macrophage Inhibitory Cytokine-1, MIC1), a member of the transforming growth factor-beta family, and Matrix Metalloproteinase-9 (MMP9), a member of the matrix metalloprotease family may be potential markers for Lewy body disorders, i.e. Parkinson's disease with (PDD) and without dementia (PDND) and Lewy body dementia (DLB). GDF15 has a prominent role in development, cell proliferation, differentiation, and repair, whereas MMP9 degrades, as a proteolytic enzyme, components of the extracellular matrix. In this study, cerebrospinal fluid GDF15 and MMP9 levels of 59 PDND, 17 PDD and 23 DLB patients, as well as of 95 controls were determined, and associated with demographic, clinical and biochemical parameters. Our analysis confirmed the already described association of GDF15 levels with age and gender. Corrected GDF15 levels were significantly higher in PDD than in PDND patients, and intermediate in DLB patients. Within Lewy body disorders, GDF15 levels correlated positively with age at onset of Parkinsonism and dementia, Hoehn & Yahr stage and cerebrospinal fluid t-Tau and p-Tau levels, and negatively with the Mini Mental State Examination. Remarkably, it does not relevantly correlate with disease duration. MMP9 was not relevantly associated with any of these parameters. Cerebrospinal GDF15, but not MMP9, may be a potential marker of and in Lewy body disorders.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Age Factors
  • Aged
  • Aged, 80 and over
  • Case-Control Studies
  • Female
  • Gene Expression
  • Growth Differentiation Factor 15 / cerebrospinal fluid
  • Growth Differentiation Factor 15 / genetics*
  • Humans
  • Lewy Body Disease / cerebrospinal fluid
  • Lewy Body Disease / diagnosis
  • Lewy Body Disease / genetics*
  • Lewy Body Disease / pathology
  • Male
  • Matrix Metalloproteinase 9 / cerebrospinal fluid
  • Matrix Metalloproteinase 9 / genetics*
  • Middle Aged
  • Parkinson Disease / cerebrospinal fluid
  • Parkinson Disease / diagnosis
  • Parkinson Disease / genetics*
  • Parkinson Disease / pathology
  • Protein Isoforms / cerebrospinal fluid
  • Protein Isoforms / genetics
  • Sex Factors
  • tau Proteins / cerebrospinal fluid
  • tau Proteins / genetics

Substances

  • GDF15 protein, human
  • Growth Differentiation Factor 15
  • MAPT protein, human
  • Protein Isoforms
  • tau Proteins
  • MMP9 protein, human
  • Matrix Metalloproteinase 9

Grants and funding

This work was supported by Deutsche Forschungsgemeinschaft and Open Access Publishing Fund of Tuebingen University, Tuebingen, Germany. Fujirebio Europe NV provided support in the form of salaries for two authors [WD, VH]. The specific roles of these authors are articulated in the ‘author contributions’ section. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.