Brain-Derived Exosomal Proteins as Effective Biomarkers for Alzheimer’s Disease: A Systematic Review and Meta-Analysis
Abstract
:1. Introduction
2. Materials and Methods
2.1. Search Strategy
2.2. Study Selection
2.3. Data Extraction
2.4. Statistical Analysis
3. Results
3.1. Characteristics of the Eligible Studies
3.2. BDE Protein Changes in AD
3.3. Meta-Analysis Results of Aβ42, t-tau, p-Y-IRS-1, p-T181-tau, p-S396-tau, and HSP70
4. Discussion
Author Contributions
Funding
Data Availability Statement
Conflicts of Interest
References
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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 |
Category | Level | Exosomal Proteins |
---|---|---|
Aβ targeted | Increase | Aβ42, APP, sAPPβ, BACE-1 |
Decrease | Aβ42, APP | |
No change | Aβ42, APP, sAPPα, sAPPβ, BACE-1, Aβ42/p-T181-tau, γ-secretase | |
Tau targeted | Increase | t-tau, p-T181-tau, p-T231-tau, p-S202-tau, p-S396-tau, p-tau/t-tau, p-T181-tau/t-tau,-tau/Aβ42 |
Decrease | t-tau | |
No change | t-tau, p-T181-tau, p-S396-tau, p-T181-tau/t-tau, t-tau/Aβ42, N-224 tau, N-123 tau, MR tau, FL tau | |
Synaptic protein | Decrease | NRGN, synaptophysin, synaptotagmin, synaptopodin, SNAP-25, AMPA4 receptor, NPTX2, NLGN1, NRXN2, p-S9-synapsin 1, synapsin 1, MOG |
Autolysosomal | Increase | cathepsin D, LAMP-1 |
No change | cathepsin D, LAMP-1 | |
Growth/trophic | Increase | GDNF |
Decrease | GDNF, FGF-2, FGF-13, HGF, IGF-1 | |
Brain insulin resistance | Increase | p-Y-IRS-1, p-S312-IRS-1, p-S312-IRS-1/p-Y-IRS-1 |
Decrease | p-Y-IRS-1 | |
No change | t-IRS-1, p-Y-IRS-1, p-S312-IRS-1, p-S312-IRS-1/p-Y-IRS-1 | |
Inflammatory related | Increase | MMP-9, TSPO |
No change | IL-6 | |
Molecular chaperone | Increase | ubiquitinylated protein |
Decrease | HSP70 | |
No change | HSP70, ubiquitinylated protein | |
Transcriptional repressor | Decrease | REST |
Cell type marker | Increase | GFAP, NF-Lch, NS-enolase |
Decrease | GFAP, GluSyn | |
No change | GluSyn, NF-Lch, NS-enolase | |
Exosome marker | Decrease | CD81 |
No change | CD81, TSG101 | |
Other | Increase | GM1 |
Decrease | GAP43, Septin-8 | |
No change | Septin-8 |
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Kim, K.Y.; Shin, K.Y.; Chang, K.-A. Brain-Derived Exosomal Proteins as Effective Biomarkers for Alzheimer’s Disease: A Systematic Review and Meta-Analysis. Biomolecules 2021, 11, 980. https://doi.org/10.3390/biom11070980
Kim KY, Shin KY, Chang K-A. Brain-Derived Exosomal Proteins as Effective Biomarkers for Alzheimer’s Disease: A Systematic Review and Meta-Analysis. Biomolecules. 2021; 11(7):980. https://doi.org/10.3390/biom11070980
Chicago/Turabian StyleKim, Ka Young, Ki Young Shin, and Keun-A Chang. 2021. "Brain-Derived Exosomal Proteins as Effective Biomarkers for Alzheimer’s Disease: A Systematic Review and Meta-Analysis" Biomolecules 11, no. 7: 980. https://doi.org/10.3390/biom11070980
APA StyleKim, K. Y., Shin, K. Y., & Chang, K.-A. (2021). Brain-Derived Exosomal Proteins as Effective Biomarkers for Alzheimer’s Disease: A Systematic Review and Meta-Analysis. Biomolecules, 11(7), 980. https://doi.org/10.3390/biom11070980