TY  - JOUR
A1  - Stoessel, Daniel
A1  - Schulte, Claudia
A1  - dos Santos, Marcia C. Teixeira
A1  - Scheller, Dieter
A1  - Rebollo-Mesa, Irene
A1  - Deuschle, Christian
A1  - Walther, Dirk
A1  - Schauer, Nicolas
A1  - Berg, Daniela
A1  - da Costa, Andre Nogueira
A1  - Maetzler, Walter
T1  - Promising Metabolite Profiles in the Plasma and CSF of Early Clinical
JF  - Frontiers in Aging Neuroscience
N2  - Parkinson's disease (PD) shows high heterogeneity with regard to the underlying molecular pathogenesis involving multiple pathways and mechanisms. Diagnosis is still challenging and rests entirely on clinical features. Thus, there is an urgent need for robust diagnostic biofluid markers. Untargeted metabolomics allows establishing low-molecular compound biomarkers in a wide range of complex diseases by the measurement of various molecular classes in biofluids such as blood plasma, serum, and cerebrospinal fluid (CSF). Here, we applied untargeted high-resolution mass spectrometry to determine plasma and CSF metabolite profiles. We semiquantitatively determined small-molecule levels (<= 1.5 kDa) in the plasma and CSF from early PD patients (disease duration 0-4 years; n = 80 and 40, respectively), and sex-and age-matched controls (n = 76 and 38, respectively). We performed statistical analyses utilizing partial least square and random forest analysis with a 70/30 training and testing split approach, leading to the identification of 20 promising plasma and 14 CSF metabolites. The semetabolites differentiated the test set with an AUC of 0.8 (plasma) and 0.9 (CSF). Characteristics of the metabolites indicate perturbations in the glycerophospholipid, sphingolipid, and amino acid metabolism in PD, which underscores the high power of metabolomic approaches. Further studies will enable to develop a potential metabolite-based biomarker panel specific for PD
KW  - biomarker
KW  - untargeted metabolomics
KW  - neurodegeneration
KW  - plasma
KW  - CSF
KW  - machinelearning
Y1  - 2018
U6  - https://doi.org/10.3389/fnagi.2018.00051
SN  - 1663-4365
VL  - 10
PB  - Frontiers Research Foundation
CY  - Lausanne
ER  -