TABLE 3.

The role of neural cell-derived exosomes in AD pathology.

	Function	Exosome-producing cells	Stimulation	Cargo	Mechanism	References
Neuron	Propagation of toxic proteins	Neurons from AD brain	–	oAβ	Mediating the propagation of oAβ between neurons and causing cytotoxicity.	Sardar Sinha et al., 2018
		Rat embryos cortical neurons and neuroblastoma N2a cells	–	Tau protein	Mediating the trans-synaptic transmission of tau protein.	Wang et al., 2017
	Clearance of toxic proteins	Primary cortical neurons from mouse and neuroblastoma N2a cells	–	–	Promoting the conformational transformation of Aβ to non-toxic amyloid fibrils and delivery to microglia for degradation.	Yuyama et al., 2012
		Primary cortical neurons from mouse brains	–	Glycosphingolipid	Capturing Aβ and decreasing the deposition of Aβ and amyloid.	Yuyama et al., 2015
		Primary cortical neurons from mouse and neuroblastoma N2a cells	Vps34 kinase inhibitor VPS34IN1 (inducing the lysosomal dysfunction of neurons)	Undigested lysosomal substrates (amyloid precursor protein C-terminal fragments, specific sphingolipids, etc.)	Mediating the clearance of toxic proteins to maintain neuronal homeostasis.	Miranda et al., 2018
Microglia	Propagation of toxic proteins	Primary cultured murine microglia	Pre-aggregated human tau 1–441 protein, ATP and LPS	Tau protein	Mediating the propagation of tau protein to neurons.	Asai et al., 2015
	Transmission of neuroinflammation	Primary mouse microglia	LPS, IL-4, IL-10	Up-regulated pro-inflammatory miRNAs and down-regulated anti-inflammatory miRNAs	Facilitating the transmission of neuroinflammation.	Gao et al., 2019
Astrocyte	Propagation of toxic proteins	Untransformed cortical adult human astrocytes	Aβ25–35	Tau and p-Tau	The spreading of tau in the brain.	Chiarini et al., 2017
	Transmission of neuroinflammation	ADEs from plasma samples of AD patients	–	IL-6, TNF-α, IL-1β, Complement proteins	Mediating neuroinflammation and neuronal damage in late AD.	Goetzl et al., 2018b
	Apoptosis of astrocytes	Cortical primary astrocytes from pups	Amyloid protein	Prostate apoptosis response 4 (PAR-4), ceramide	Promoting neuronal apoptosis by activating caspase 3.	Wang et al., 2012