Lipid Rafts: Linking Alzheimer's Amyloid-β Production, Aggregation, and Toxicity at Neuronal Membranes
Figure 1
Lipid rafts facilitate the production, aggregation, neuronal binding and toxicity of Aβ oligomers. (a) The Aβ peptide is produced by the lipid raft dependent sequential cleavage of APP, first by BACE1 and then by the γ-secretase complex; (b) Lipid raft components including cholesterol and sialic acid-containing gangliosides promote the aggregation of Aβ to form soluble oligomers; (c) Aβ oligomers bind to specific neuronal receptors within pathogenic lipid rafts, including PrPC and the NMDA and mGluR5 receptors. The resulting perturbations in neuronal function and survival underlie the memory impairments and cognitive decline which characterise Alzheimer’s disease.
