Here, we analyzed AD-related phenotypes of cultured neurons derived from human iPSC (hiPSC) lines of different apoE genotypes, including gene-edited isogenic and apoE-deficient lines. We also tested the effects of gene editing to convert apoE4 into apoE3 and of a small-molecule structure corrector to render apoE4 apoE3-like. Our data demonstrate that apoE4 induces AD-related pathological phenotypes, due to a gain of toxic effects, specifically in human neurons, which can be dramatically ameliorated by a small-molecule apoE4 structure corrector.
