Representative studies of urine biomarker analysis

Targetsubstance 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.

Exp Neurobiol 2020;29:325~333 https://doi.org/10.5607/en20042
© Exp Neurobiol