γ-secretase as a target for Alzheimer's disease

Abstract

The two characteristic pathological features of Alzheimer's disease (AD) found in the brain are extracellular amyloid plaques and intraneuronal fibrillary tangles, the former being composed primarily of the 4-kDa amyloid β-peptide (Aβ) and the latter containing paired helical filaments of the microtubule-associated protein tau (Hardy, Duff, Hardy, Perez-Tur, & Hutton, 1998). While dominant mutations in the tau gene can cause other forms of dementia (Lee, Goedert, & Trojanowski, 2001), missense mutations in the Aβ precursor protein (APP) alter Aβ production and cause familial early onset AD (Selkoe, 2001).