Table 1.

AD model summary

Structure	Advantages	Limitations	References
Cortical model based on 3D hydrogel gel (neurons and astrocytes)	• Deposition of amyloid plaques	• Absence of vascular cells	Choi et al. (2014); Kim et al. (2015b); Jorfi et al. (2018)
	• Accumulation of pTau	• Absence of flow
	• High-throughput possible	• Cell lines with FAD mutations
	• Short time of culture
Cortical model based on 3D hydrogel gel (neurons, astrocyte and microglia)	• Deposition of amyloid plaques	• Absence of vascular cells	Park et al. (2018)
	• Accumulation of pTau	• Absence of flow
	• Microglial migration assay	• Cell lines
	• Short time of culture
NVU capillary model based on microfluidic chip (EC, astrocytes and neurons)	• CAA and amyloid plaque deposition	• Cell lines	Shin et al. (2019)
	• Live imaging	• Absence of mural cells
	• Vascular flow	• Non-contractile
	• EC permeability assays
	• Short time of culture
Cortical model based on organoids (neurons and astrocytes)	• IPSC from AD patient	• Low through put	Lee et al. (2016); Gonzalez et al. (2018)
	• Deposition of amyloid plaques	• Long time of culture
	• Accumulation of pTau	• Absence of vascular cells
	• Apoptosis assay	• Absence of flow
Capillary model based on 3D hydrogel (EC, pericytes and astrocytes)	• IPSC from patient	• No perfusion	Blanchard et al. (2020)
	• CAA	• Exogenous Ab
	• Deposition of BM	• Absence of neuron
	• Self-organization of the vasculature	• Non-contractile?
	• Short time of culture
Arterial model based on tissue engineering (EC, SMC and astrocytes)	• CAA	• Recombinant Ab	Robert et al. (2017)
	• Vascular flow	• Absence of neuron
	• Trans-endothelial transport	• Low throughput
	• Primary cells	• Long time of culture
	• Monocyte perfusion	• Non-contractile
	• Live media sampling in lumen and ablumen
NVU arterial model based on tissue engineering (EC, SMC, astrocytes and neurons)	• CAA	• Low throughput	Robert et al. (2020)
	• Accumulation of pTau	• Long time of culture
	• Neuronal and glial biomarkers	• Non-contractile
	• Trans-endothelial transport	• Umbilical origin of the vascular cells
	• Vascular flow
	• Live media sampling in lumen and ablumen

3D: Three-dimensional; AD: Alzheimer’s disease; Aβ: amyloid beta; BM: basement membrane; CAA: cerebral amyloid angiopathy; EC: endothelial cells; FAD: early onset familial AD; IPSC: induced pluripotent stem cells; NVU: neurovascular unit; pTau: phosphorylated Tau; SMC: smooth-muscle cells.