Table 2 The cerebrospinal fluid biomarkers of amyotrophic lateral sclerosis disease
Biomarkers | Sample size | Method | Role | Highlight | Cutoff point | Area under curve (AUC) | Reference |
|---|---|---|---|---|---|---|---|
Non exosomal biomarker | |||||||
TDP-43 | ALS: 36 Control: 24 | Western blot (Thermo Fisher Scientific, Waltham, Catalog# 711,051) And immuno-infrared sensor | RNA regulation | 89% Sensitivity and 83% Specificity for ALS versus healthy controls ALS: 1639.5 ± 2.6 cm− 1 SD Normal: 1646 ± 5.5 cm− 1 SD | 1643 cm− 1 (Immuno-infrared sensor) | 0.93 | Beyer et al. 2021 [38] |
MCP-1 | ALS: 77 Control: 13 | Bio-PlexProTM commercial kit (Bio-Rad Laboratories, Inc., Hercules, CA, USA) | Chemokine | No correlation between duration and the clinical stages of the disease MCP-1 level increased (234.89 pg/mL vs. 160.95 pg/mL, P = 0.011) | Not mentioned | Not mentioned | MartÃnez et al. 2020 [66] |
MIP-1β | ALS: 77 Control: 13 | Bio-PlexProTM commercial kit (Bio-Rad Laboratories, Inc., Hercules, CA, USA) | Chemokine | No correlation between duration and the clinical stages of the disease The MIP-1β level increased (10.68 pg/mL vs. 4.69 pg/mL, P < 0.0001) | Not mentioned | Not mentioned | MartÃnez et al. 2020 [66] |
MFG-E8 | ALS: 19 Control: 15 | sandwich ELISA kit | Anti-inflammatory | MFG-E8 level increased 2503.70 (1294.79) pg/ml compared to normal participants 1332.23 (910.37) pg/ml | Not mentioned | 0.77 | Yang et al. 2020 [65] |
NFL | ALS: 19 Control: 15 | sandwich ELISA kit | Axonal transport, shaping cells | NFL level increased 151.12 (9.88) pg/ml compared to normal participants 140.90 (12.85) pg/ml | Not mentioned | 0.77 | Yang et al. 2020 [65] |
PGRN | ALS: 16 Control: 17 | human PGRN ELISA kit | Inflammation | The PGRN level was 4.1 ± 1.5 ng in ALS compared to 4.0 ± 1.1 ng in normal participants | Not mentioned | Not mentioned | Feneberg et al. 2016 [62] |
CD14 | ALS: 40 Control: 19 | R&D Systems® ELISA Kits | Inflammatory markers secreted from Hepatocytes | Elevated in ALS comparted to normal participants (ALS mean ~ 150ng/mL, normal ~ 110ng/mL) | Not mentioned | Not mentioned | Beers DR et al. 2020 [68] |
Exosomes biomarkers | |||||||
miR-124-3p (exosomes) | ALS: 6 Control: 9 | Total Exosome Isolation Reagent (#4,484,453, Thermo Fisher Scientific) | Anti-inflammatory | Elevated levels in ALS patients than controls. a significant association between exosomal miR-124-3p levels and ALS disease clinical stage | Not mentioned | Not mentioned | Yelick et al. 2020 [86] |
CUEDC2 (exosomal mRNA) | ALS: 4 Control: 4 | exoRNeasy Serum/Plasma Midi Kit (QIAGEN, Hilden, Germany) Agencourt RNAdvance Tissue Kit (Beckman Coulter, CA, USA) | Correlated with oxidative stress response, unfolded protein response | Upregulated in patients with ALS. Potential candidate for ALS-related disease biomarker | Not mentioned | Not mentioned | Otake et al. 2019 [87] |