Table 2.
Descriptive statistics of the diagnostic metrics of studies included in the meta-analysis
| Study | Biomarkers | Sensitivity (95% CI) | Specificity (95% CI) | FPR (95% CI) | DOR (95% CI) | posLR (95% CI) | negLR (95% CI) |
|---|---|---|---|---|---|---|---|
| PD vs control | |||||||
| Shi et al. 2014 [38] | nEVs α-syn | 0.701 (0.659–0.740) | 0.529 (0.484–0.573) | 0.471 (0.427–0.516) | 2.64 (2.02–3.44) | 1.49 (1.33–1.66) | 0.565 (0.481–0.663) |
| Shi et al. 2014 [38] | nEVs α-syn/total plasma α-syn | 0.712 (0.670–0.750) | 0.500 (0.456–0.544) | 0.500 (0.456–0.544) | 2.47 (1.89–3.22) | 1.42 (1.28–1.58) | 0.577 (0.488–0.681) |
| Shi et al. 2016 [37] | nEVs tau | 0.701 (0.659–0.740) | 0.529 (0.484–0.573) | 0.350 (0.287–0.419) | 2.55 (1.70–3.83) | 1.65 (1.32–2.07) | 0.648 (0.535–0.787) |
| Zhao et al. 2019 [50] | nEVs DJ-1/total plasma DJ-1 | 0.595 (0.485–0.696) | 0.823 (0.724–0.891) | 0.177 (0.109–0.276) | 6.82 (3.28–14.17) | 3.36 (2.02–5.58) | 0.492 (0.370–0.655) |
| Zhao et al. 2019 [50] | nEVs α-syn + DJ-1 | 0.823 (0.724–0.891) | 0.519 (0.411–0.626) | 0.481 (0.374–0.589) | 5.01 (2.42–10.36) | 1.71 (1.33–2.20) | 0.341 (0.203–0.575) |
| Niu et al. 2020 [25] | nEVs α-syn | 0.973 (0.907–0.993) | 0.541 (0.428–0.649) | 0.459 (0.351–0.572) | 42.35 (9.67–185.60) | 2.12 (1.65–2.72) | 0.050 (0.013–0.199) |
| Niu et al. 2020 (early-stage PD vs HC) [25] | nEVs α-syn | 0.095 (0.047–0.183) | 0.568 (0.454–0.674) | 0.432 (0.326–0.546) | 0.14 (0.06–0.34) | 0.22 (0.10–0.46) | 1.595 (1.290–1.972) |
| Zou et al. 2020 [52] | nEVs α-syn, Linc-POU3F3, and plasma GCase activity | 0.708 (0.637–0.770) | 0.831 (0.770–0.879) | 0.169 (0.121–0.230) | 11.95 (7.19–19.87) | 4.20 (2.99–5.90) | 0.351 (0.277–0.446) |
| Si et al. 2019 [39] | nEVs α-syn | 0.661 (0.530–0.771) | 0.714 (0.585–0.816) | 0.286 (0.184–0.415) | 4.87 (2.19–10.85) | 2.31 (1.47–3.64) | 0.475 (0.318–0.710) |
| Jiang et al. 2020 [17] | nEVs α-syn | 0.850 (0.812–0.881) | 0.740 (0.696–0.780) | 0.260 (0.220–0.304) | 16.07 (11.38–22.71) | 3.27 (2.77–3.86) | 0.203 (0.161–0.257) |
| Agliardi et al. 2021 [1] | nEVs α-syn/STX-1A | 0.861 (0.763–0.923) | 0.819 (0.715–0.891) | 0.181 (0.109–0.285) | 28.14 (11.46–69.08) | 4.77 (2.89–7.87) | 0.169 (0.094–0.304) |
| Agliardi et al. 2021 [1] | nEVs α-syn/VAMP-2 | 0.750 (0.639–0.836) | 0.931 (0.848–0.970) | 0.069 (0.030–0.152) | 40.20 (14.02–115.30) | 10.80 (4.59–25.42) | 0.269 (0.179–0.403) |
| Jiang et al. 2021 [16] | nEVs α-syn | 0.819 (0.782–0.851) | 0.740 (0.699–0.777) | 0.260 (0.223–0.301) | 12.90 (9.47–17.57) | 3.15 (2.70–3.69) | 0.244 (0.201–0.298) |
| Jiang et al. 2021 [16] | nEVs α-syn/Clusterin | 0.861 (0.827–0.889) | 0.869 (0.836–0.896) | 0.131 (0.104–0.164) | 40.99 (28.32–59.34) | 6.57 (5.21–8.30) | 0.160 (0.128–0.201) |
| Dutta et al. 2021 [11] | nEVs α-syn, oEVs/nEVs α-syn, and CD81 concentration | 0.712 (0.618–0.790) | 0.625 (0.529–0.712) | 0.375 (0.288–0.471) | 4.11 (2.30–7.35) | 1.90 (1.44–2.50) | 0.462 (0.330–0.646) |
| Yan et al. 2022 [48] | EVs and nEVs α-syn | 0.837 (0.748–0.899) | 0.663 (0.562– 0.751) | 0.337 (0.249–0.438) | 10.1 (5.01–20.38) | 2.48 (1.84– 3.35) | 0.246 (0.151–0.400) |
| Taha et al. 2023 [43] | nEVs α-syn, oEVs/nEVs α-syn, oEVs pS129-α-syn, and CD81 concentration | 0.718 (0.610–0.806) | 0.897 (0.810–0.947) | 0.103 (0.053–0.190) | 22.27 (9.22–53.82) | 7.00 (3.58–13.69) | 0.314 (0.219–0.451) |
| Taha et al. 2023 [43] | nEVs α-syn, oEVs/nEVs α-syn, oEV tau, and CD81 concentration | 0.419 (0.329–0.515) | 0.848 (0.767–0.904) | 0.152 (0.096–0.233) | 4.01 (2.08–7.75) | 2.75 (1.66–4.55) | 0.685 (0.572–0.822) |
| Sharafeldin et al. 2023 [35] | nEVs α-syn | 0.650 (0.495–0.779) | 0.950 (0.835–0.986) | 0.050 (0.0138–0.165) | 35.3 (7.39–168.4) | 13.0 (3.30–51.1) | 0.368 (0.240–0.565) |
| Jiao et al. 2023 [18] | nEVs α-syn, plasma CCL2, and CXCL12 | 0.680 (0.583–0.763) | 0.940 (0.875–0.972) | 0.060 (0.0277–0.124) | 33.3 (13.2–84.0) | 11.3 (5.16–24.9) | 0.340 (0.255–0.455) |
| Wang et al. 2023 [46] | GLT-1 + and SYN211 + EVs and GLT-1 + and MFJR14 + EVs | 0.818 (0.760–0.865) | 0.895 (0.846–0.929) | 0.10 (0.070–0.15) | 38.25 (21.75–62.27) | 7.77 (5.21–6.10) | 0.20 (0.15–0.27) |
| Chen et al. 2023 [5] | nEVs Transferrin R-Protein | 0.857 (0.762–0.918) | 0.701 (0.592–0.792) | 0.30 (0.21–0.41) | 14.09 (6.31–31.46) | 2.87 (2.01–4.09) | 0.36 (0.11–0.36) |
| PD vs MSA | |||||||
| Yu et al. 2020 [49] | oEVs α-syn | 0.621 (0.501–0.729) | 0.818 (0.709–0.893) | 0.182 (0.107–0.292) | 7.38 (3.32–16.41) | 3.42 (1.98 –5.89) | 0.463 (0.333–0.643) |
| Yu et al. 2020 [49] | oEVs α-syn/total plasma α-syn | 0.530 (0.412–0.646) | 0.848 (0.743–0.916) | 0.152 (0.0844–0.257) | 6.32 (2.76–14.48) | 3.50 (1.89–6.47) | 0.554 (0.42098–0.729) |
| Jiang et al. 2020 [17] | nEVs α-syn + Clusterin | 0.958 (0.929–0.976) | 0.920 (0.883–0.946) | 0.0796 (0.0536–0.117) | 266.96 (130.21–547.34) | 12.04 (8.13–17.84) | 0.045 (0.026–0.079) |
| Jiang et al. 2021 [16] | nEVs α-syn | 0.820 (0.728–0.886) | 0.865 (0.779–0.921) | 0.135 (0.0788–0.221) | 29.28 (12.97–66.08) | 6.08 (3.56 –10.39) | 0.208 (0.132–0.326) |
| Jiang et al. 2021 [16] | nEVs α-syn/Clusterin | 0.910 (0.833–0.954) | 0.640 (0.537–0.732) | 0.360 (0.268–0.463) | 18.04 (7.74–42.01) | 2.53 (1.90 –3.36) | 0.140 (0.071–0.277) |
| Dutta et al. 2021 [11] | nEVs α-syn, oEVs/nEVs α-syn, and CD81 concentration | 0.893 (0.819–0.939) | 0.864 (0.785–0.917) | 0.136 (0.0827–0.215) | 53.17 (22.91–123.37) | 6.57 (4.02–10.74) | 0.124 (0.070–0.217) |
| Taha et al. 2023 [43] | nEVs α-syn, oEVs/nEVs α-syn, oEVs pS129-α-syn, and CD81 concentration | 0.803 (0.700–0.877) | 0.895 (0.806–0.946) | 0.105 (0.0543–0.194) | 34.57 (13.71–87.18) | 7.63 (3.92–14.83) | 0.221 (0.139–0.349) |
| Taha et al. 2023 [43] | nEVs α-syn, oEVs:nEVs α-syn, oEVs tau, and CD81 concentration | 0.946 (0.879–0.977) | 0.707 (0.607–0.790) | 0.293 (0.210–0.393) | 41.89 (15.30–114.65) | 3.22 (2.34–4.44) | 0.077 (0.032–0.182) |
| Wang et al. 2023 [46] | GLT-1 + SYN211 + EVs and GLT-1 + and MFJR14 + EVs | 0.784 (0.713–0.842) | 0.895 (0.837–0.935) | 0.10 (0.065–0.16) | 31.14 (16.33–59.37) | 7.50 (4.68–12.01) | 0.241 (0.177–0.327) |
| PD vs PSP and CBS | |||||||
| Jiang et al. 2020 (FTD included) [17] | nEVs α-syn + Clusterin | 0.918 (0.888–0.941) | 0.958 (0.935–0.974) | 0.042 (0.026–0.065) | 258.31 (142.92–466.86) | 22.09 (13.95–34.97) | 0.086 (0.062–0.118) |
| Jiang et al. 2021 [16] | nEVs α-syn/Clusterin | 0.999 (0.990–1.000) | 0.948 (0.925–0.965) | 0.052 (0.035–0.075) | 18,209.24 (1105.43–299,953.43) | 19.39 (13.29–28.30) | 0.001 (0.000–0.017) |
| Meloni et al. 2023 [24] | nEVs α-syn/tau | 0.941 (0.881–0.972) | 0.671 (0.579–0.752) | 0.329 (0.248–0.421) | 32.82 (13.53–79.57) | 2.86 (2.19–3.75) | 0.087 (0.041–0.186) |
| MSA vs control | |||||||
| Yu et al. 2020 [49] | oEVs α-syn | 0.836 (0.727–0.907) | 0.711 (0.590–0.808) | 0.289 (0.192–0.410) | 12.53 (5.33–29.44) | 2.89 (1.94–4.31) | 0.231 (0.130–0.410) |
| Yu et al. 2020 [49] | oEVs α-syn/total plasma α-syn | 0.523 (0.403–0.641) | 0.555 (0.433–0.670) | 0.445 (0.330–0.567) | 1.37 (0.68–2.74) | 1.18 (0.82–1.68) | 0.859 (0.613–1.204) |
| Dutta et al. 2021 [11] | nEVs α-syn, oEVs/nEVs α-syn, and CD81 concentration | 0.956 (0.897–0.982) | 0.838 (0.755–0.897) | 0.162 (0.103–0.245) | 112.27 (38.05–331.28) | 5.91 (3.79–9.21) | 0.053 (0.021–0.130) |
| Taha et al. 2023 [43] | nEVs α-syn, oEVs/nEVs α-syn, oEVs pS129-α-syn, and CD81 concentration | 0.992 (0.928–0.999) | 0.960 (0.880–0.988) | 0.040 (0.012–0.120) | 3025.00 (142.28–64,314.30) | 25.00 (7.42–84.25) | 0.008 (0.001–0.131) |
| Taha et al. 2023 [43] | nEVs α-syn, oEVs:nEVs α-syn, oEVs tau, and CD81 concentration | 0.880 (0.800–0.931) | 0.922 (0.851–0.961) | 0.078 (0.039–0.149) | 86.70 (32.97–228.04) | 11.27 (5.65–22.49) | 0.130 (0.075–0.224) |
| RBD vs control | |||||||
| Jiang et al. 2020 [17] | nEVs α-syn | 0.610 (0.530–0.684) | 0.810 (0.742–0.865) | 0.188 (0.133–0.258) | 6.67 (4.00–11.48) | 3.25 (2.27–4.64) | 0.479 (0.386–0.595) |
| Yan et al. 2022 [48] | nEVs α-syn | 0.936 (0.894–0.962) | 0.717 (0.652–0.773) | 0.282 (0.226–0.346) | 38.33 (20.3–72.5) | 3.32 (2.67–4.13) | 0.087 (0.051–0.148) |
| Sharafeldin et al. 2023 [35] | nEVs α-syn | 0.682 (0.511–0.814) | 0.985 (0.870–0.998) | 0.0151 (0.00158–0.129) | 139.3 (7.76–2500.0) | 45.0 (2.84–711.4) | 0.323 (0.196–0.533) |
95% CI 95% confidence interval; CCL2 C–C motif chemokine ligand 2; CBS corticobasal syndrome; CXCL12 C-X-C motif chemokine ligand 12; DJ-1 protein deglycase DJ-1; DOR diagnostic odds ratio; EV extracellular vesicle; FPR false-positive rate; FTD frontotemporal dementia; GCase glucocerebrosidase; HC healthy control; Linc-POU3F3 long intergenic noncoding RNA POU3F3; MSA multiple system atrophy; negLR negative likelihood ratio; nEVs neuronal extracellular vesicles; oEVs oligodendroglial extracellular vesicles; PD Parkinson's disease; posLR positive likelihood ratio; PSP progressive supranuclear palsy; pS129-α-syn phosphorylated Serine 129 α-synuclein; RBD REM behavior disorder; α-synuclein α-syn; STX-1A syntaxin-1A; VAMP-2 vesicle associated membrane protein 2