One of the first indications that E2 was protective against AD was obtained when E2 was found to stimulate the processing of APP, at the level of the α-secretase enzyme, preventing the generation of Aβ, generating a soluble non-amyloidogenic APP (32); therefore, E2 blocks the amyloid plaques formation (32), a key neuropathological lesion in AD (31). The gene discussed is APP; the disease is Alzheimer disease.