The DIO mice in our study exhibited markedly reduced vascular responsiveness to ACh, which was mirrored in RC-fed mice by raising the circulating level of Aβ42 to that observed in plasma of HF-fed mice, directly by Aβ42 infusion or indirectly through increased BACE1-dependent cleavage of human mutant APP in transgenic mouse models. This evidence concerns the gene APP and hydrops fetalis.