Amyloid beta-protein and lipid rafts: focused on biogenesis and catabolism

Cerebral accumulation of amyloid beta-protein (Ab) is thought to play a key role in the molecular pathology of Alzheimer's disease (AD). Three secretases (beta-, gamma-, and alpha-secretase) are proteases that control the production of A beta from amyloid precursor protein. Increasing evidence suggests that cholesterol-rich membrane microdomains termed 'lipid rafts' are involved in the biogenesis and accumulation of A beta as well as A beta-mediated neurotoxicity gamma-Secretase is enriched in lipid rafts, which are considered an important site for A beta generation. Additionally, A beta-degrading peptidases located in lipid rafts, such as neprilysin, appear to play a role in A beta catabolism. This mini-review focuses on the roles of lipid rafts in the biogenesis and catabolism of A beta, covering recent research on the relationship between lipid rafts and the three secretases or A beta-degrading peptidases. Furthermore, the significance of lipid rafts in A beta aggregation and neurotoxicity is briefly summarized.