Lastly, our findings in hiPSC-derived neurons provide a proof of concept that correcting the pathogenic conformation of apoE4 is a viable therapeutic approach for apoE4-related AD1,8,36–38. Treating apoE4/4 hiPSC-derived neurons with the apoE4 structure corrector PH00236–38 ameliorated the detrimental effects of apoE4 on tau phosphorylation, Aβ production, and GABAergic neuron degeneration in a dose-dependent manner. These findings warrant further development of apoE4 structure correctors and, ultimately, testing in clinical trials.
