Exploring the Role of PSEN Mutations in the Pathogenesis of Alzheimer’s Disease

Alzheimer's disease (AD) is the most common cause of dementia. Mutations of presenilin (PSEN) genes that encode presenilin proteins have been found as the vital causal factors for early-onset familial AD (FAD). AD pathological features such as memory loss, synaptic dysfunction, and formation of plaques have been successfully mimicked in the transgenic mouse models that coexpress FAD-related presenilin and amyloid precursor protein (APP) variants. γ-Secretase (GS) is an enzyme that plays roles in catalyzing intramembranous APP proteolysis to release pathogenic amyloid beta (Aβ). It has been found that presenilins can play a role as the GS's catalytic subunit. FAD-related mutations in presenilins can modify the site of GS cleavage in a way that can elevate the production of longer and…