Table 1.

Exosomes as AD biomarkers in discussed studies

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	[54]
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	[55]
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	[56]
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	[58]
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.	[60]

↑ 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