Chapter 4 γ-Secretase — Regulated Signaling and Alzheimer ' s Disease

Alzheimer’s disease (AD) is an incurable and progressive neurodegenerative disorder and the most common form of dementia that occurs with aging. The main hallmarks of this disease are the extracellular deposition of amyloid plaques and the intracellular aggregation of tangles in the brain [1, 2]. Although the causes of both the onset and progression of AD are still uncertain, much evidence, including results of genetic analysis, indicates that amyloid precursor protein (APP) itself and its proteolytic processing are responsible for AD. Indeed, familial forms of AD (FAD) have mutations [3] or a duplication of the APP gene [4] or mutations in the presenilin1 or 2 (PS1 or PS2) genes [5-7] that code for a catalytic component of the γ-secretase complex [8].