TABLE 1.

The study of exosome contents in AD biomarkers.

Molecule	Object	Source	Expression	Potential target/mechanism	Significance	References
Cathepsin D, LAMP-1, ubiquitinylated protein	Human	serum	Up	autophagic-lysosomal dysfunction	It is a pathological change that can appear 10 years before the onset of AD.	Goetzl et al., 2015
HSP70	Human	serum	It declines in the early stages of AD and is reversed in the middle and late stages.	HSP70 acts on proteins that accumulate in the brain.	May mark the extent of synaptic dysfunction or neurodegeneration.	Goetzl et al., 2015; Chanteloup et al., 2019
SNAP-25	Human	serum	Down	-	It is related to the disease progression of AD and directly reflects the characteristic of synaptic loss during the progression of AD.	Agliardi et al., 2019
miR-9-5p, miR-598	Human	CSF	Down	It plays a potential regulatory role in amyloid proteins, stress pathways, and neurotrophic signaling.	These miRNAs may be potential biomarkers for AD.	Riancho et al., 2017
miR-342-3p, miR-342-5p, miR-150-5p, miR-23b-3p, miR-29b-3p	Human	serum	Down	-	These miRNAs are collectively altered in the disease, rather than being a single biomarker.	Lugli et al., 2015
miR-124, miR-146a, miR-155, miR-21, miR-125b	-	Culture of cell	Up	These miRNAs can be transported from cell to cell via exosome form to mediate mRNA transcription and aggravate the inflammatory response.	MiR-21 plays an important role in signal transduction between microglial cells and neurons, especially in neuroinflammation.	Fernandes et al., 2018
hsa-miR-101-3p miR-1306, hsamiR-106b	Human	serum	Up Down	Hsa-miR-101 can target and regulate APP mRNA, thereby reducing APP level in hippocampal neurons and promoting Aβ accumulation. Hsa-miR-1306 can target to regulate APP mRNA and increase the synthesis of APP. The down-regulation of HSAMIR-106b is associated with transforming growth factor-β signaling.	Using differential miRNAs to make a random forest model for clinical classification prediction has high sensitivity and specificity.	Cheng et al., 2015
miR-125b-5p, miR-451a, miR-605-5p miR-16-5p	Human	CRF	Down in the first stages of the disease and increase in moderate and advanced stages. Down in the Young-onset AD.	Overexpression of miR-125b-5 leads to tau hyperphosphorylation and neurotoxicity and MiR-451a plays a role in neuroinflammation.	MiR-16-5p is differentially expressed in late-onset AD and Young-onset AD and maybe a special biomarker of Young-onset AD.	McKeever et al., 2018