Table 1.

Current and future disease-modifying therapeutic targets for AD.

Decrease Aβ production
• β-secretase inhibition
• γ-secretase inhibition or modulation
• α-secretase enhancement
Decrease Aβ aggregation
• Decrease metal ion–mediated fibrilization
• Decrease oligomer formation via reduction of Aβ monomers
• Decrease plaques by blocking β-pleated sheet formation
Increase Aβ degradation
• Insulin-degrading enzyme (IDE) activation
• Neprilysin activation
Increase Aβ clearance
• “Active” vaccination with truncated Aβ peptide
• Passive immunization with monoclonal antibody against Aβ epitope
• Passive immunization with antibody against specific confirmational forms of Aβ (such as oligomers, protofibrils, or plaque)
Decrease tau and neurofibrillary tangle formation
• Prevent tau hyperphosphorylation
• Decrease tau aggregation
• Stabilize microtubules
• Active and passive immunization against tau
Neuroprotection or neuroregeneration
• Antioxidant and other agents to preserve metabolic and/or mitochondrial function
• Antiapoptotic agents
• Decrease inflammatory damage
• Nerve growth factor enhancement
• Stem cell–based neuron replacement