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Table 1 Exosomes as AD biomarkers in discussed studies

From: Mesenchymal stem cell-derived exosome: a promising alternative in the therapy of Alzheimer’s disease

Source Body fluid Isolation methods Validation techniques Direction of protein change Ref.
Neuronal Plasma EXOQ + anti-L1CAM immunocapture TEM, NTA ADC and AD: P-T181-tau, P-S396-tau, and Aβ1–42 ↑, NRGN, REST ↓ compared to CNC and stable MCI patients [53]
Neurally Plasma or serum EXOQ + anti-NCAM immunocapture NTA AD: total Tau, P-T181-tau, P-S396-tau and Aβ1–42 ↑compared to controls
FTD: P-T181-tau and Aβ1–42 ↑ compared to controls
Neuronal Plasma
or CSF
EXOQ + anti-NCAM immunocapture TEM, WB AD: Aβ42, T-tau, and P-T181-tau ↑ compared to aMCI and control groups
The level of each exosomal biomarker was highly correlated with that in CSF
Neuronal Plasma EXOQ + anti-L1CAM immunocapture NTA, TEM, WB AD and FTD: synaptophysin, synaptopodin, synaptotagmin-2, and neurogranin ↓ compared to controls
AD: GAP43, synapsin 1 ↓ synaptotagmin, synaptophysin, and neurogranin were correlated with MMSE or ADAS-cog
Neurally Plasma EXOQ + anti-L1CAM immunocapture NTA AD: cathepsin D, LAMP-1, ubiquitinylated proteins ↑, and HSP70 ↓ compared to controls and FTD [57]
Neuronal Plasma EXOQ + anti-L1CAM immunocapture NTA, TEM, WB AD:NPTX2, NRXN2α, AMPA4, NLGN1 ↓
Preclinical period: NRXN2α, AMPA4, and NLGN1 ↓ compared to controls
Astrocyte Plasma EXOQ + anti-ACSA-1 immunocapture NTA, TEM, WB AD: complement proteins, IL-6, TNF-α, IL-1β ↑; complement regulatory proteins (CD59, CD46, DAF), complement receptor type 1 ↓ compared to controls [59]
Astrocyte Plasma EXOQ + anti-ACSA-1 immunocapture NTA AD: BACE-1, (s)APPβ ↑, GDNF ↓ compared to controls
FTD: compared to controls n. d.
  1. ↑ higher; ↓ lower; n. d. no difference compared to control, EXOQ ExoQuick exosome precipitation solution, L1CAM neural adhesion protein, TEM transmission electron microscope, NTA Nanoparticle Tracking Analysis, MCI mild cognitive impairment, ADC MCI converting to AD, REST repressor element 1-silencing transcription factor, NRGN neurogranin, ADAS-cog AD assessment scale-cognitive subscale, CNC cognitively normal controls, FTD frontotemporal dementia, GAP43growth-associated protein 43, MMSE Mini-Mental State Examination, LAMP-1 lysosome-associated membrane protein 1, HSP70 heat-shock protein 70, ACSA-1 antihuman glutamine aspartate transporter, NPTX2 neuronal pentraxin 2, NRXN2α neurexin 2α, AMPA4 GluA4-containing glutamate, NLGN1 receptor and neuroligin 1, TNF-α tumor necrosis factor-α, DAF decay-accelerating factor, BACE-1 β-site amyloid precursor protein-cleaving enzyme 1, (s)APP soluble amyloid precursor protein, GDNF glial-derived neurotrophic factor