ET-1 induced stroke in transgenic amyloid precursor protein mice, thus simulating the interaction between stroke and amyloid pathology and showing that subclinical stroke could induce an increase in localized amyloid pathology [68]; this is consistent with the clinical finding that stroke patients with underlying amyloid pathology could develop a more severe and rapid cognitive decline over three years than those without underlying amyloid pathology [82]. This evidence concerns the gene APP and stroke disorder.