Having discovered a designer peptide that directly halts apoE binding to N-terminal APP and markedly limits apoE-mediated Aβ production (12), we tested whether 6KApoEp therapy for 3 months modifies AD-relevant phenotypes in amyloid β-protein precursor/presenilin 1 (APP/PS1) mice that express each human apoE isoform of apoE2, apoE3, or apoE4 under the endogenous regulatory control (designated as APP/PS1/E2, APP/PS1/E3, or APP/PS1/E4 mice; alternatively designated as APP/PS1/E2/E3/E4 mice). Here, PSEN1 is linked to Alzheimer disease.