APOE Allele Switching in a Novel Transgenic Mouse Model as a Therapeutic Approach for Alzheimer’s Disease

Individuals homozygous for the ε4 allele of Apolipoprotein E (APOE) face up to a 15‐fold increase in Alzheimer’s Disease (AD) risk. In comparison, those carrying two ε2 alleles have nearly a 99.6% reduction in risk. Given APOE’s strong risk profile and multitude of effects, APOE itself has emerged as a promising therapeutic target. CRISPR‐Cas9 technology has been used to successfully edit APOE in vitro, where iPSC‐derived glia and neurons edited from ε4 to ε3 show pronounced transcriptional and phenotypic changes. However, whether the putatively beneficial effects of switching to APOE2 holds true in in vivo models has yet to be fully determined.