APP and Alzheimer disease: The central role of amyloid beta due to mutations in genes of amyloid beta precursor protein APP and its endoproteases was unarguably recognized in the pathogenesis of early onset AD; however, the missing strong correlation between amyloid senile plaque deposits and severity of sporadic AD [87], and failure of attempts to therapeutically target amyloid beta-associated pathology in AD have opened more space to investigate tau protein involvement in AD [6,219].