Gene mutation and oligomerization in Alzheimer’s disease

Abstract

Alzheimer’s disease (AD) is the most common neurodegenerative disorder characterized by memory loss and cognitive dysfunction with a strong genetic predisposition. Pathological characteristics of AD are the presence of extracellular amyloid plaques composed of amyloid-β(Aβ) as well as intracellular neurofibrillary tangles containing hyper-phosphorylated Tau protein. The prior research focused on the insoluble amyloid-β and Tau protein; however, suppressing their expression had no significant clinical effect on AD. Common mutations in AD include Swedish double mutation (K670N and M671L), London (V717I), Indiana (V717F), and Dutch mutation (E693Q). However, with progress in research, much evidence suggests that it is not the insoluble protein aggregate but the soluble Aβ oligomer and Tau oligomer (Aβ-O and Tau-O) that are the major etiology of AD. These factors could propagate like prion to promote the formation of senile plaques and neurofibrillary tangles, thereby causing AD. Key words: Alzheimer’s disease; Genetic predisposition; Gene mutation; Oligomers