APP and Alzheimer disease: Thus, although recent studies in iPSC-derived cerebral organoids derived from LOAD patients show that Aβ clearance mechanism rather than APP processing is altered, independently on ApoE4 status [15], previous studies have shown that ApoE4 may interfere with Aβ metabolism, either by directly binding to the peptide or preventing its clearance, which promotes its deposition in toxic forms and potentiates AD development.