PT  - JOURNAL ARTICLE
AU  - Rebecca L Pinals
AU  - Li-Huei Tsai
TI  - Building in vitro models of the brain to understand the role of <em>APOE</em> in Alzheimer’s disease
AID  - 10.26508/lsa.202201542
DP  - 2022 Nov 01
TA  - Life Science Alliance
PG  - e202201542
VI  - 5
IP  - 11
4099  - https://www.life-science-alliance.org/content/5/11/e202201542.short
4100  - https://www.life-science-alliance.org/content/5/11/e202201542.full
SO  - Life Sci. Alliance2022 Nov 01; 5
AB  - Alzheimer’s disease (AD) is a devastating, complex, and incurable disease that represents an increasingly problematic global health issue. The etiology of sporadic AD that accounts for a vast majority of cases remains poorly understood, with no effective therapeutic interventions. Genetic studies have identified AD risk genes including the most prominent, APOE, of which the ɛ4 allele increases risk in a dose-dependent manner. A breakthrough discovery enabled the creation of human induced pluripotent stem cells (hiPSCs) that can be differentiated into various brain cell types, facilitating AD research in genetically human models. Herein, we provide a brief background on AD in the context of APOE susceptibility and feature work employing hiPSC-derived brain cell and tissue models to interrogate the contribution of APOE in driving AD pathology. Such models have delivered crucial insights into cellular mechanisms and cell type–specific roles underlying the perturbed biological functions that trigger pathogenic cascades and propagate neurodegeneration. Collectively, hiPSC-based models are envisioned to be an impactful platform for uncovering fundamental AD understanding, with high translational value toward AD drug discovery and testing.