Histologically, the AD brain is marked by the extracellular deposition of senile beta-amyloid (Aβ) plaques—in early-onset FAD, this accumulation has been traced to abnormalities in the genes encoding amyloid precursor protein (APP) or intramembrane protease presenilin 1 and 2 (PS1, PS2). This evidence concerns the gene APP and Alzheimer disease.