Table 1.
Representative studies of urine biomarker analysis
| Target substance |
Disease | Detection method | Target | Number of case | Conclusion* | Reference | |
|---|---|---|---|---|---|---|---|
| Disease | Control | ||||||
| Metabolites | AD | UPLC coupled with quadruple time-of-flight MS | Mouse | 30 | 30 | 5-hydroxyindoleacetic acid↑ and change of other 25 metabolites | [39] |
| LC–MS/MS targeting 3-HPMA, ELISA for AC-Acro | Human | 32 | 74 | 3-HPMA/Cre↓ AC-Acro/Cre↓ |
[85] | ||
| Head-space GC/MS | Mouse | 38 | 34 | 1-octen-3-ol↓ | [86] | ||
| PD | Non-targeted metabolic profiling and ELISA | Human | 92 | 65 | Biopyrrine ↑ | [87] | |
| ELISA for kynurenine | Human | 41 | 41 | Kynurenine ↑ | [34] | ||
| LC-MS base | Human | 106 | 104 | Cortisol↑, 11-deoxycortisol↑, 21- deoxycortisol↑, histidine↑, urocanic acid↑, imidazoleacetic acid↑, hydroxy-phenylacetic acid↑ | [15] | ||
| LC-MS & GC-MS base | Human | 92 | 65 | Change of 18 metabolites (alanine, leucine, isoleucine, aminobutyric acid, hydroxytryptophan, cortisol, etc.) | [14] | ||
| Nucleic acids | AD | Ultra-performance LC--tandem MS | Human | 53 | 27 | 8-OHdG↑ and 8-OHdG/2dG↑ | [44] |
| PD | ELISA for 8-OHdG | Human | 72 | 48 | (8-OHdG)/creatinine↑ | [76] | |
| Protein | AD | LC-MS/MS | Mouse | NS | NS | Kallikrein-1 (↑ or ↓ depending on mouse age) | [7] |
| ELSIA for AD7c-NTP | Human | 66 | 134 | AD7c-NTP↑ | [52, 54, 56, 57, 88] | ||
| LC-MS/MS | Human | 18 | 18 | Change of 73 proteins (>2-fold↑) and 36 proteins (<0.5-fold↓) | [16] | ||
| 2 gene expression data of brain samples → iTRAQ of urine samples | Human | 20 (urine) | 20 (urine) | SPP1↓, GSN↑, and IGFBP7↑ | [51] | ||
| PD | EV-MS/MS | Human | Discovery:28 replication:51 | Discovery:22 replication:57 | SNAP23↑, and calbindin↑ | [6] | |
| Scalable and sensitive MS | Human | Cohort 1: 35 HC, 16 NMC, 40 iPD, 28 LRRK2 PD; Cohort 2: 26 HC, 37 NMC, 29 iPD, 23 LRRK2 PD |
PPIB↑, apolipoproteins↑, VGF↓ in iPD; ALPI↑, (HEXA, HEXB, GM2A and GCase)↑ in LRRK2 PD |
[58] | |||
| ELISA for oligomer, filament and total α-syn | Human | 21 | 11 | Specific filament form of α-synuclein↑ | [13] | ||
| Western blot | Human | 26 | 21 | DJ-1↑ (in Male only) | [8] | ||
*Some targets are omitted because of space limit.
NS, not specified; 2dG, 2’-deoxyguanosine; 3-HPMA, 3-HPMA3-Hydroxypropyl mercapturic acid; Cre, creatinine; AC-Acro, amino acid-conjugated acrolein; 8-OHdG, 8-hydroxy-2’-deoxyguanosine; AD7c-NTP, AD-associated Neuronal Thread Protein; EV, Extracellular Vesicle; ELISA, Enzyme-Linked ImmunoSorbent Assay; HC, Healthy Controls; NMC, Non-Manifesting LRRK2 G2019S Carriers; iPD, idiopathic PD patients; LRRK2 PD, manifesting PD patients with LRRK2 G2019S.