Besides the interesting issues already discussed at length and in depth, the data bring to mind the problem of why N-terminally directed antibodies—and particularly those against the EFRH epitope as demonstrated by Beka Solomon and coworkers—are most efficient in passive vaccination. The explanation is that the N-terminal is "dangling" outside the amyloid fibers and thereby accessible.
Then I wonder about antibodies that react about two orders of magnitude less well with pE-Aβ (i.e., Aβ3-42 peptide, starting with pyroglutamyl at residue Glu-3), than with wt-Aβ (Gardberg et al., 2007). Are these acting not or less well on pE-Aβ in human brain and thereby explaining differences in efficacy of passive vaccination in mouse models and human patients?
Gardberg AS, Dice LT, Ou S, Rich RL, Helmbrecht E, Ko J, Wetzel R, Myszka DG, Patterson PH, Dealwis C. Molecular basis for passive immunotherapy of Alzheimer's disease. Proc Natl Acad Sci U S A. 2007 Oct 2;104(40):15659-64. Abstract
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