While it is possible that the lower Aβ42/40 ratio present in iPSC-neuronal cultures bearing the ApoE4 allele is secondary to the accumulation of Aβ42 in insoluble aggregates, this finding may also be a result of other drivers of AD pathology in the ApoE 3/3 AD iPSC cohort. This evidence concerns the gene APOE and Alzheimer disease.