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

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.

Serum Growth Differentiation Factor 15 in Parkinson Disease

“…A second possible source of discrepancy between Maetzler et al [34] and the present study is that in the former most patients (approximately 70%) with Lewy body disorders (including nondemented PD patients, PD patients with dementia, and patients with Lewy body dementia) had relatively mild motor dysfunction (Hoehn and Yahr stage 1—2). GDF15 positively correlated with disease severity by Hoehn and Yahr stage, which may partly explain the relatively lower CSF GDF15 level in patients with Lewy body disorders in the study by Maetzler et al [34].…”

“…GDF15 positively correlated with disease severity by Hoehn and Yahr stage, which may partly explain the relatively lower CSF GDF15 level in patients with Lewy body disorders in the study by Maetzler et al [34]. …”

“…In 2016, Maetzler et al [34] reported that patients with PD dementia had levels of cerebrospinal fluid (CSF) GDF15 that were 17% (7-28%) higher than those of a control group of individuals without neurological disease. However, in the present study, the mean GDF15 level of the PD group was approximately 2-fold that of the control group.…”

“…However, their [34] article did not mention the criteria for the controls in the study of CSF GDF15 other than that they were without neurological disease. Nevertheless, both studies showed that GDF15 correlated with PD severity (indicated by the UPDRS-III score in our study and the Hoehn-Yahr stage in the study by Maetzler et al), independent of disease duration.…”

Subregional differences in astrocytes underlie selective neurodegeneration or protection in Parkinson's disease models in culture

“…A role for GDF15 in PD is supported by the recent discovery that greater levels of GDF15 in the cerebrospinal fluid of PD patients are correlated with a later age of disease onset (Maetzler et al, ). Likewise, early studies showed that exogenous GDF15 is trophic to embryonic midbrain DA neurons in vitro and pretreatment with GDF15 decreases motor dysfunction in a 6‐hydroxydopamine rat model (Strelau et al, ).…”