. Epitope and isotype specificities of antibodies to beta -amyloid peptide for protection against Alzheimer's disease-like neuropathology. Proc Natl Acad Sci U S A. 2003 Feb 18;100(4):2023-8. PubMed.

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  1. This is a study on a quite impressive scale that compares different isotypes of anti-Abeta antibodies with respect to efficacy in attenuating amyloid loads in PDAPP mice. The conclusion is anti-Abeta IgG with high affinity for Fc receptors are more effective then those with lower affinity for FcR. This supports this group's hypothesis that microglial uptake of anti-Abeta:Abeta complexes is important in Abeta immunotherapy.
    Our group is currently preparing a manuscript that is not easily reconcilable with these findings. Our data has also been presented at recent meetings. We find that Abeta immunotherapy is equally effective in Tg2576 mice crossed into an FcR gamma knockout background mice as it is in wt Tg2576 mice. Our studies would seem to preclude FcR mediated uptake of anti-Abeta:Abeta complexes as a factor in determing efficacy of immunization.

    Although there was no good correlation between efficacy in the bard study and binding affinites of the antibodies to soluble or aggregated Abeta, perhaps there is some other property of the anibodies that is more closely associated with efficacy? For example binding to oligomers, ability to cross the blood brain barrier, etc....