Similarly, work in the 5XFAD mouse model of AD, which overexpress APP with three familial AD mutations (K607N, M671L, and I716V) and double mutated PSEN1 (M146L/L286V), also supported the presence of a progressive disruption to the left ventricle EF which advanced with the severity of disease and was accompanied by cardiac fibrosis [205]. Here, APP is linked to Alzheimer disease.