Table 1.
Characteristics of the eligible studies.
| Study | Location | Specimen | Method | Patients | Sample (M/F) | Age (y) (M ± SD) | MMSE (M ± SD) | BDE Proteins | |||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Case | Control | Case | Control | Case | Control | ||||||
| Fiandaca et al. 2015 [28] | USA | Plasma | ExoQuick/ELISA | AD | 30/27 | 30/27 | 79.5 ± 6.1 | 79.6 ± 6.0 | Aβ42, t-tau, p-T181-tau, p-S396-tau | ||
| Goetzl et al. 2015 [29] | USA | Plasma | ExoQuick/ELISA | AD (include MCI) | 13/13 | 13/13 | 75.4 ± 7.9 | 75.8 ± 7.9 | 22.5 ± 1.5 | cathepsin D, LAMP-1, HSP70, ubiquitinylated protein | |
| Kapogiannis et al. 2015 [30] | USA | Plasma | ExoQuick/ELISA | AD | 13/13 | 13/13 | 74.3 ± 7.5 | 74.3 ± 7.5 | t-IRS-1, p-S312-IRS-1, p-Y-IRS-1, p-S312-IRS-1/p-Y-IRS-1 | ||
| Dementia | 10 | 20.5 ± 2.2 | |||||||||
| Abner et al. 2016 [31] | USA | Plasma | ExoQuick/ELISA | AD | 5/5 | 10/10 | 77.6 | 77.6 | 29.4 ± 0.8 | Aβ42, p-T181-tau, NRGN, cathepsin D, REST | |
| Goetzl et al. 2016a [32] | USA | Plasma | ExoQuick/ELISA | AD | 6/6 | 6/6 | 74.4 ± 2.0 | 74.4 ± 2.0 | 26.3 ± 1.0 | 29.8 ± 0.1 | Synaptophysin, synaptotagmin, synaptopodin, NRGN, p-S9-synapsin 1, GAP43, synapsin 1, MOG, GAP43 |
| AD2 (after diagnosis of dementia) | 2/7 | 2/7 | 87.8 ± 2.5 | 82.2 ± 2.3 | 21.4 ± 1.6 | 28.3 ± 1.0 | |||||
| Goetzl et al. 2016b [33] | USA | Plasma | ExoQuick/ELISA | AD (include amnestic mild cognitive impairment and early dementia) | 12 | 10 | Aβ42, sAPPα, sAPPβ, BACE-1, γ-secretase, p-T181-tau, p-S396-tau, GDNF, GFAP, GluSyn, NF-Lch, NS-enolase, CD81, Septin-8 | ||||
| Winston et al. 2016 [34] | USA | Plasma | ExoQuick/ELISA | AD | 11/9 | 10 | 75.4 ± 6.8 | 17.7 ± 0.7 | Aβ42, p-T181-tau, p-S396-tau, NRGN, REST | ||
| Guix et al. 2018 [35] | USA | Plasma | ExoQuick/ELISA | AD (mild) | 3/7 | 3/7 | 75.6 ± 12.9 | 75.9 ± 8.7 | 75.6 ± 12.9 | 29.7 ± 0.5 | Aβ42, p-T181-tau, MR tau, FL tau |
| AD (moderate) | 4/6 | 75.6 ± 12.9 | 75.6 ± 12.9 | ||||||||
| Goetzl et al. 2018 [36] | USA | Plasma | ExoQuick/ELISA | AD | 12/16 | 12/16 | 73.1 ± 1.4 | 73.2 ± 1.5 | 25.6 ± 0.8 | 29.7 ± 0.1 | AMPA4 receptor, NPTX2, NLGN1, |
| AD2 (after diagnosis of dementia) | 10/8 | 10/8 | 78.2 ± 1.8 | 70.1 ± 1.7 | 20.2 ± 1.5 | 28.3 ± 1.0 | NRXN2 | ||||
| Jia et al. 2019 [37] | China | Plasma | ExoQuick/ELISA | AD | 39/42 | 35/37 | 65 ± 6 | 64 ± 5 | 19.6 ± 3.1 | 29.3 ± 1.2 | Aβ42, p-T181-tau |
| Agliardi et al. 2019 [38] | Italy | Serum | ExoQuick/ELISA | AD | 8/16 | 4/13 | 77.7 ± 1.4 | 76.5 ± 1.5 | 21.9 ± 0.9 | 28.7 ± 0.4 | SNAP-25 |
| Chanteloup et al. 2019 [39] | Spain | Plasma | ExoQuick/ELISA | AD | 21 | 13 | 77.1 ± 8.2 | 75.2 ± 6.7 | HSP70 | ||
| Cicognola et al. 2019 [40] | Sweden | Serum | ExoQuick/SIMOA | AD | 4 | 4 | 79.5 | 67 | >15 | N-224 tau, N-123 tau | |
| Goetzl et al. 2019 [41] | USA | Plasma | ExoQuick/ELISA | AD | 9/15 | 9/15 | 73.1 ± 1.6 | 73.1 ± 1.8 | 26.1 ± 0.9 | 29.3 ± 0.2 | AMPA4 receptor, FGF-2, FGF-13, HGF, IGF-1, GluSyn, CD81 |
| AD2 (after conversion to moderate dementia) | 7/8 | 7/8 | 84.5 ± 1.7 | 80.2 ± 1.8 | 24.3 ± 0.9 | 29.4 ± 0.6 | |||||
| Kapogiannis et al. 2019 [42] | USA | Plasma | ExoQuick/ELISA, SIMOA | AD (future) | 60/68 | 112/110 | 79.1 ± 7.0 | 76.2 ± 7.4 | 27.5 ± 1.8 | 28.4 ± 1.8 | t-tau, p-T181-tau, p-T231-tau, p-S312-IRS-1, p-Y-IRS-1, TSG101 |
| Serum | AD | 17/18 | 6/23 | 74.0 ± 8.7 | 72.1 ± 7.9 | 23.9 ± 3.0 | 29.8 ± 0.6 | ||||
| Gu et al. 2020 [43] | China | Plasma | ExoQuick/ELISA | AD | 8/23 | 5/10 | 68.6 ± 8.0 | 64.8 ± 6.0 | 15.9 ± 6.6 | 27.7 ± 1.7 | Aβ42, p-T181-tau, p-S396-tau, IL-6, MMP-9, CD81 |
| Jia et al. 2020 [44] | China | Plasma | ExoQuick/ELISA | AD | 59/62 | 74/86 | 66 ± 5 | 54 ± 6 | 20.7 ± 2.9 | 29.1 ± 1.1 | Synaptotagmin, NRGN, SNAP-25, GAP43 |
| Nam et al. 2020 [45] | Korea | Serum | ExoQuick/ELISA | AD | 3/17 | 17/9 | 76.6 ± 1.3 | 73.9 ± 0.9 | 16.6 ± 0.5 | 27.7 ± 0.2 | Aβ42, t-tau, p-T181-tau, p-S202-tau, p-tau/t-tau |
| Perrotte et al. 2020 [46] | Canada | Plasma | Exosome isolation kit/Luminex | AD (mild) | 1/11 | 3/9 | 75.6 ± 1.3 | 68.8 ± 1.5 | 24.0 ± 0.5 | 29.4 ± 0.3 | Aβ42, APP, Aβ42/p-T181-tau, t-tau, p-T181-tau, p- T181-tau/t-tau, t-tau/Aβ42 |
| AD (moderate) | 4/8 | 79.1 ± 1.1 | 19.9 ± 1.4 | ||||||||
| AD (severe) | 2/10 | 83.0 ± 1.6 | |||||||||
| Picciolini et al. 2021 [47] | Italy | Plasma | Chromatography using qEV columns/ELISA | AD | 4/6 | 5/5 | 73.9 ± 3.0 | 62.6 ± 2.0 | TSPO, GM1 | ||
AD: Alzheimer’s disease, ELISA: enzyme-linked immunosorbent assay, MCI: mild cognitive impairment, MMSE: mini-mental state examination, SIMOA: single molecule array.