Evidence for impaired amyloid β clearance in Alzheimer's disease

Alzheimer's disease (AD) is a common neurodegenerative disease characterized by the accumulation of extracellular plaques and intracellular tangles. Recent studies support the hypothesis that the accumulation of amyloid beta (A beta) peptide within the brain arises from an imbalance of the production and clearance of A beta. In rare genetic forms of AD, this imbalance is often caused by increased production of A beta. However, recent evidence indicates that, in the majority of cases of AD, A beta clearance is impaired. Apolipoprotein E (ApoE), the dominant cholesterol and lipid carrier in the brain, is critical for A beta catabolism. The isoform of ApoE and its degree of lipidation critically regulate the efficiency of A beta clearance. Studies in preclinical models of AD have demonstrated that coordinately increasing levels of ApoE and its lipid transporter, ABCA1, increases the clearance of A beta, suggesting that this pathway may be a potential therapeutic target for AD.