Mutations in the amyloid precursor protein (APP) gene have also been associated with AD because they trigger the interaction between ASK1 and APP under cellular stress, as shown in 2-year-old 5XFAD ASK1-deficient mice (containing five AD-linked mutations) with improved cognitive function and decreased soluble amyloid-β in the brain [62]. This evidence concerns the gene MAP3K5 and Alzheimer disease.