Generation and validation of APOEknockout human iPSC-derived cerebral organoids

Apolipoprotein E (apoE) is a major lipid carrier in the brain and closely associated with the pathogenesis of Alzheimer's disease (AD). Here, we describe a protocol for efficient knockout of APOEin human induced pluripotent stem cells (iPSCs) using the CRISPR-Cas9 system. We obtain homozygous APOEknockout (APOE-/-) iPSCs and further validate the deficiency of apoE in iPSC-derived cerebral organoids. APOE-/-cerebral organoids can serve as a useful tool to study apoE functions and apoE-related pathogenic mechanisms in AD.