PSEN1 and Alzheimer disease: Although the mechanisms underlying increased deposition of Aβ and phosphorylated tau proteins in the brain of LOAD patients are unknown, several mouse models that overexpress mutant human amyloid precursor protein (APP) or APP plus mutant human presenilin 1 or mutant form of human microtubule-associated protein tau P301S have been generated and used to study the mechanisms, whereby Aβ and hyperphosphorylated tau proteins promote AD pathophysiology [24,25,40,41,49,70,71,72,73,74,75,76].