APP and Alzheimer disease: Here, it is shown that partial hepatic loss of Aβ in transgenic AD mice immunized with Aβ antibody 3D6 and its absence in amyloid precursor protein (APP) knockout mice (APP‐KO), as well as in human liver spheroids with APP knockdown upregulates classical hallmarks of fibrosis, smooth muscle alpha‐actin, and collagen type I. Aβ absence in APP‐KO and deficiency in immunized mice lead to strong activation of transforming growth factor‐β (TGFβ), alpha secretases, NOTCH pathway, inflammation, decreased permeability of liver sinusoids, and epithelial‐mesenchymal transition.