Klotho is an amyloid precursor protein (APP)- and APP-like Protein 2 (APLP2)-dependent gene that is regulated by the large secreted ectodomain fragment soluble (APPsβ) [33], and therefore, it may play a role in the development of Alzheimer’s disease. This evidence concerns the gene APLP2 and early-onset autosomal dominant Alzheimer disease.