Although a number of mechanisms have been proposed for how Aβ immunotherapy might work to prevent deposition, or clear, Aβ from the brain, no definitive answer has emerged. Some active and passive immunization studies show correlation between the efficacy of immunization and the ability of anti-Aβ monoclonal antibodies (mAbs) to recognize amyloid. Others show quite the opposite—certain mAbs that effectively reduce Aβ loads bind preferentially to monomeric Aβ. Such data raise the possibility that there may be multiple ways in which anti-Aβ antibodies influence amyloid deposition and other AD-like pathologies. However, important as it is, few studies were actually dedicated to the question of, How does anti-Aβ immunization work?
In our mechanism of immunization study (Levites et al., 2006) we have shown that, at least in mice, the following statements are true:
- Binding of mAbs to Aβ significantly prolongs the half-life of plasma Aβ.
- Very little free anti-Aβ mAb actually enters the brain.
- Anti-Aβ mAb:Aβ complexes...