Decreased Clearance of CNS β-Amyloid in Alzheimer's Disease

摘要

Alzheimer's disease (AD) is characterized by increased amounts of soluble and in-sohible β-amyloid (Aβ), predominantly in the form of Aβ42 in amyloid plaques and Aβ40 in amyloid angiopathy. The amyloid hypothesis proposes that AD is caused by an imbalance between Aβ production and clearance (1), resulting in increased amounts of Aβ in various forms such as monomers, oligomers, insoluble fibrils, and plaques in the central nervous system (CNS). High levels of Aβ then initiate a cascade of events culminating in neuronal damage and death manifesting as progressive clinical dementia of the AMieimer's type (2). In rare cases of AD, genetic alterations increase the production of Aβ (3). However, Aβ dysregula-tion in the far more common late-onset "sporadic" AD is less well understood. Possible mechanisms of increased Aβ production for late-onset AD include alterations in gamma or beta secretase activity.