Figure 2.

The Aβ cascade and potential therapeutics that have recently failed in human clinical trials. A highly schematic drawing illustrating the main steps involved in Aβ production and deposition as thought to occur in the AD brain. Production begins following cleavage of APP by β- or γ-secretases followed by the formation of oligomers and fibrils that eventually deposit into extracellular plaques. Broadly, therapeutics shown are targeted to either Aβ formation or clearance mediated by microglia. In addition, the connection of Aβ to eventual synapse loss and cell death is linked through tangle development.