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 | Martínez 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 | Martínez 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] |