Amyloid-based Intervention Strategies—Stopping AD at the Start

Many researchers are focusing on attacking AD at its source by developing new drug candidates that interfere at various points along the amyloid cascade (Figure 8).[19, 24]

It is their hope that successful intervention early in the disease process will prevent downstream pathological processes and delay the onset, slow the progression, or even stop AD before it starts. These so-called disease-modifying treatments may also help improve symptoms by rescuing surviving neurons.

Several anti-amyloid agents are already in various stages of testing to determine their safety, efficacy, and potential to modify the course of AD. These include:

1. 1. β-Secretase inhibitors—to block the first enzymatic cleavage of APP [19, 24]
2. gamma-Secretase inhibitors—to block the second enzymatic cleavage of APP and the subsequent formation of Aβ and its toxic fragments [19, 24]
3. Selective Aβ42-Lowering Agents (SALAs)—to reduce production of the toxic Aβ42 fragment through modulation of gamma-secretase [19, 24]
4. Immunotherapies—to stimulate the host immune system to recognize and attack Aβ or to provide antibodies that prevent Aβ plaque deposition or enhance plaque clearance [3, 19, 24]
5. Anti-aggregation agents—to prevent Aβ fragments from aggregating or to clear aggregates once they are formed [19, 24]

Figure 8. The Aβ pathway and targeted sites for anti-amyloid treatments that may have the potential to modify the course of AD. Adapted with permission.[24] ©2003. American Society for Clinical Investigation. All rights reserved.