The amyloid hypothesis proposes that the amyloid beta peptide (Aβ) aggregation (senile plaque) in the “extracellular space” of the human brain is at the top of pathological cascade and that removal of the “extracellular Aβ” should ameliorate and/or reverse the AD pathology as a whole and improve the symptoms of AD patients. Here, APP is linked to Alzheimer disease.