Table 2.

Disease modeling approach using brain organoids.

Disease model	Type of organoid	Phenotypes	Cell	References
Neurodevelopmental disease
Microcephaly	Forebrain organoid	• Reduction in overall size of organoid • Premature differentiation of NPCs	hiPSCs	Lancaster et al., 2013
Microcephaly (caused by ZIKA virus)	NPCs, Neurosphere brain organoid	• Reduction in overall size of organoid • Cell disruption and death in neurospheres	hiPSCs	Garcez et al., 2016
	Forebrain organoid	• Preferentially infection in NPCs at the early stage organoid • Reduction in overall size and VZ layer thickness	hiPSCs	Qian et al., 2016
	NPCs brain organoid	• Premature differentiation of NPCs • Reduction in VZ and cortical layer • Defect in centrosomal structure of NPCs	hiPSCs	Gabriel et al., 2017
	Cerebral organoid	• Activation of Toll-like receptor 3 (TLR3) after ZIKA infection • Dysregulation of neurogenesis genes • Reduction in overall size and neuroepithelium	hESCs	Dang et al., 2016
Lissencephaly (Miller-Dieker syndrome)	Cerebral organoid	• Reduction in overall size of organoid • Increased apoptosis of NESCs • Decreased migration of neurons • Mitotic delay in oRGCs	hiPSCs	Bershteyn et al., 2017
	Forebrain organoid	• Reduction in overall size of organoid • Division plane of vRGCs was changed from symmetric to asymmetric • Altered microtubule network organization of vRGCs	hiPSCs	Iefremova et al., 2017
Rett syndrome (RTT)	Cerebral organoid	• Increased number of proliferating NPCs • Expanded VZ area • Impaired neurogenesis and maturation	hiPSCs	Mellios et al., 2018
Neuropsychiatric disease
Schizophrenia	Cerebral organoid	• Increased NPC proliferation • Abnormal premature migration of NPCs • Malformation in cortical region	hiPSCs	Stachowiak et al., 2017
Neurodegenerative disease
Alzheimer's disease (AD)	hNPCs embedded in matrigel	• Amyloid-β deposition • Hyperphosphorylation of tau protein • Attenuated symptoms by β- or γ-secretase inhibitor treatment	hNPCs	Choi et al., 2014
	Scaffold-free 3D brain organoid model	• Amyloid-β deposition and hyperphosphorylation of tau protein occurred sequentially over time • Attenuated symptoms by β- or γ-secretase inhibitor treatment	hiPSCs	Raja et al., 2016
	Cerebral organoid	• Amyloid-β deposition • Hyperphosphorylation of tau protein • Similar phenotypes of Down syndrome(DS) brain organoid	hiPSCs	Gonzalez et al., 2018
Parkinson's disease (PD)	Midbrain organoid (Sporadic PD model with LRRK2-muatation)	• Decreased DA neuron and mature neuron • Abnormal localization of α-synuclein • Suggesting a relationship between TXNIP gene and sporadic PD	hiPSCs	Kim et al., 2019