Table 1 The plasma/serum biomarkers of amyotrophic lateral sclerosis disease
Biomarkers | Sample size | Method | Role | Highlight | Cutoff point | Area under curve (AUC) | Reference |
|---|---|---|---|---|---|---|---|
Non exosomal biomarker | |||||||
miRNA-206 | ALS: 27 Control: 13 | miRCURY RNA Isolation Kit Biofluids (Exiqon Cat #EX300112) ExiLENT SYBRR Green master mix (Exiqon Cat #203,421) and Exiqon microRNAs specific primers | Transcriptional regulation of gene expression | Increased value was correlated with a better prognosis | ≤ 145.1 copies/200 µl serum | 0.9917 | Dobrowolny et al. 2021 [49] |
miR-133a | ALS: 27 Control: 13 | miRCURY RNA Isolation Kit Biofluids (Exiqon Cat #EX300112) ExiLENT SYBRR Green master mix (Exiqon Cat #203,421) and Exiqon microRNAs specific primers | Transcriptional regulation of gene expression | Increased value was correlated with a better prognosis | ≤ 108.2 copies/200 µl serum | 0.8088 | Dobrowolny et al. 2021 [49] |
miR-151a-5p | ALS: 27 Control: 13 | miRCURY RNA Isolation Kit Biofluids (Exiqon Cat #EX300112) ExiLENT SYBRR Green master mix (Exiqon Cat #203,421) and Exiqon microRNAs specific primers | Transcriptional regulation of gene expression | Increased value was correlated with a better prognosis | ≤ 11,183 copies/200 µl serum | 0.8846 | Dobrowolny et al. 2021 [49] |
NFL | ALS: 30 Control: 20 | The human NF-light assay (Cat No: 102,258) kits | Axonal transport and shaping cells | Significantly higher levels of serum NFL in patients with ALS and correlated with disease progression: 63.3 (46.9–98.1) pg/mL than in healthy controls: 5.3 (4.5–7.1) pg/mL | 14.3 pg/mL | 1 | Sugimoto et al. 2020 [58] |
CD14 | ALS: 100 Control: 60 | R&D Systems® ELISA Kits | An inflammatory marker secreted from Hepatocytes | Elevated in ALS compared to normal participants (ALS mean ~ 3.2 µg/mL, normal ~ 2.6 µg/mL) | 2.73 µg/ml | 0.93 | Beers DR et al. 2020 [68] |
C reactive protein | ALS: 100 Control: 60 | R&D Systems® ELISA Kits | An inflammatory marker secreted from Hepatocytes | Elevated in ALS compared to normal participants (ALS mean ~ 5 µg/mL, normal ~ 1 µg/mL) | 4.53 µg/ml | 0.965 | Beers DR et al. 2020 [68] |
Lipopolysaccharide binding protein | ALS: 100 Control: 60 | R&D Systems® ELISA Kits | Inflammatory markers secreted from Hepatocytes | Elevated in ALS compared to normal participants (ALS mean ~ 40 µg/mL, normal ~ 20 µg/mL) | 40.8 µg/ml | 0.966 | Beers DR et al. 2020 [68] |
Exosomes Biomarkers | |||||||
miR-146a-5p, miR-199a-3p, miR-151a-3p, miR-151a-5p, and miR-199a-5p (exosomes) | ALS: 20 Control: 20 | ExoRNeasy Serum/Plasma Kit (cat. no. 77,023, Qiagen, Hilden, Germany) LightCycler® 480 Real-Time PCR System (Roche, Basel, Switzerland) | Not mentioned | Upregulated in ALS patients compared to control participants based on 2−(ΔΔCt) | Not mentioned | Not mentioned | Banack et al., 2020 [52] |
miR-4454, miR-10b-5p, and miR-29b-3p (exosomes) | ALS: 20 Control: 20 | ExoRNeasy Serum/Plasma Kit (cat. no. 77,023, Qiagen, Hilden, Germany) LightCycler® 480 Real-Time PCR System (Roche, Basel, Switzerland) | Not mentioned | Downregulated in ALS patients compared to control participants based on 2−(ΔΔCt) | Not mentioned | Not mentioned | Banack et al., 2020 [52] |
miR-27a-3p (exosomes) | ALS: 10 Control: 20 | ExoEasy Maxi, exoQuick Kit, and qRT-PCR | Not mentioned | Downregulated in ALS patients compared to control participants | Not mentioned | Not mentioned | Xu et al. 2018 [85] |
CORO1A (exosomes) | ALS: 30 Control: 33 | Sandwich enzyme-linked immunoassay (ELISA) (05657, Y-s Biotechnology, China) | Blocks autophagic flux and fusion with lysosomes | Increased 5.3-fold higher in ALS compared to controls. Increased with disease progression | Not mentioned | Not mentioned | Zhou et al. 2022 [26] |
TDP-43 (exosomes) | ALS: 18 | EXObuffer (Biovesicle Inc.) | RNA regulation | An increase was observed in TDP-43 over time | Not mentioned | Not mentioned | Chen et al. 2020 [24] |
NFL (exosomes) | ALS: 18 | Biotin-labeled anti-NFL monoclonal antibody (IBL, Hamburg, Germany) | Axonal transport and shaping cells | The concentration was increased in the rapid progression ALS group | Not mentioned | Not mentioned | Chen et al. 2020 [24] |