Table 1.
Overview of metabolomic studies in PD clinical research. LCECA, liquid chromatography electrochemistry array; LID, L-DOPA-induced-dyskinesia; BCAA, branched chain amino acid.
| Article | Analytical Platform | Statistics | Patients (#) | Pathway/Compound | |
|---|---|---|---|---|---|
| Increased in PD | Decreased in PD | ||||
| Bogdanov et al., 2008 [56] | LCECA | PLS-DA t-test |
PD (60), controls (25) | B: Glutathione metabolism (GSH) | B: Purine metabolism (uric acid ) |
| Johansen et al., 2009 [51] | LCECA | PLS-DA | PD (41), PD-LRRK2 (12), healthy-LRRK2 (21), controls (25) | B: Purine metabolism (uric acid, hypoxanthine) | |
| Ahmed et al., 2009 [55] | H-NMR | PLS-DA, ANOVA |
PD (43), controls (37) | B: Energy metabolism (pyruvate) | B: Energy metabolism (TCA metabolites, creatinine) |
| Roede et al., 2013 [70] | LC-MS2 + | (O)PLS-DA t-test |
PD rapid progress (39), PD slow progress (41), Controls (20) | B: Polyamine metabolism (N8-acetylspermidine) | |
| LeWitt et al., 2013 [53] | LC-MS2 +/− GC-MS |
t-test ROC curve |
PD (48), controls (57) | C: Kynurenine metabolism (3-HK/KYNA) | C: Acetylated amino acids, C: glutathione metabolism (GSSG) |
| Trupp et al., 2014 [54] | GC-MS | (O)PLS-DA | PD (20), controls (20) | B: Amino acids (methionine, threonine, alanine, serine), glutathione metabolism (pyroglutamate), ketoleucine | C: Energy metabolism (creatinine), tryptophan metabolism (tryptophan) B: FA metabolism (C16 and C18) |
| Öhman and Forsgren 2015 [87] | H-NMR | Multivariate, univariate | PD (10), controls (10) | C: Amino acids (alanine), energy metabolism (creatinine), sugars (mannose) | |
| Luan et al., 2015 [67] | LC-MS +/− | (O)PLS-DA ROC curve |
PD (106), controls (104) | U: BCAA, Glycine derivatives, histidine metabolism, tryptophan/kynurenine metabolism, phenylalanine metabolism , purine metabolism, steroidogenesis | |
| Luan et al., 2015 [76] | LC-MS +/− GC-MS |
(O)PLS-DA | PD (92), controls (65) | ||
| Hatano et al., 2016 [66] | LC-MS +/− GC-MS |
t-test | PD (35), controls (15) | U: Phenylalanine metabolism (phenylacetate) | B: Bilirubin/biliverdin, tryptophan metabolism |
| Wuolikainen et al., 2016 [72] | LC-MS +/− GC-MS |
(O)PLS-DA | PD (22), ALS (22), controls (28) | B and C: Amino acids (alanine) C: BCAA (leucine, isoleucine) |
|
| LeWitt et al., 2017 [86] | LC-MS +/−
GC-MS |
Multivariate t-test |
PD (49); collected twice with an interval of up to 2 years | B: FA metabolism (medium-long chain FA), phenylalanine metabolism (aspartylphenylalanine, benzoate), serine metabolism (serine) | B: Purine metabolism (inosine) |
| Burté et al., 2017 [71] | LC-MS2 +/− GC-MS |
PCA (O)PLS-DA |
PD early stage (41), Controls (40) | B: FA metabolism (acylcarnitine), histidine metabolism (1-methylhistamine) | |
| Havelund et al., 2017 [52] | LC-MS+ | ANOVA | PD (26), PD-LID (10), controls (14) | B: Kynurenine metabolism (3-HK/KYNA) | B and C: Kynurenine metabolism (anthranilic acid ) |
2 Data-dependent MS/MS; +/− shows which MS ion mode was used; B/C/U: indicate in which biofluid (B: blood, C: CSF, U: urine) the compound/pathway was found.