APOE and Alzheimer disease: Given that GABAergic dysfunction is commonly found in the frontal cortex of AD patients carrying the apolipoprotein epsilon 4 allele and in animal models of AD with APOE4 knock-in, it is possible that the abnormal calcium oscillation in PFC-like spheroids with APOE4/4 GABAergic neurons is a result of altered GABAergic transmission40–42,45–47.