Abstract
Aβ vaccination has been shown to induce remarkable clearance of brain amyloid plaques
in mouse models of Alzheimer's disease (AD). However, the extent to which antibody-mediated
Aβ clearance is affected by predominant formation of Aβ42 over Aβ40 is unclear. Here
we demonstrate for the first time that in a mouse model carrying the human APP mutations
KM670/671NL and the human PS1 mutation P166L, Aβ vaccination does not result in plaque
clearance. This was in spite of the strong T- and B-cell immune responses evoked under
the DR1501 genetic background and the activation of microglia at sites of Aβ plaques.
Our findings suggest the existence of antibody-resistant forms of Aβ deposits in the
brain consisting of primarily Aβ42, and shed light on the mechanisms of antibody-dependent
amyloid clearance as well as novel therapeutic strategies for AD.
Abbreviations:
AD (Alzheimer's disease), Aβ (amyloid beta-peptide), CNS (central nervous system), APP (amyloid precursor protein), CFA (complete Freund's adjuvant), FAD (familial Alzheimer's disease), HLA (human leukocyte antigen), IFA (incomplete Freund's adjuvant), PS1 (preseneline-1), SAD (sporadic Alzheimer's disease)Keywords
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Article info
Publication history
Published online: April 12, 2012
Accepted:
March 18,
2012
Received in revised form:
March 15,
2012
Received:
December 20,
2011
Identification
Copyright
© 2012 Elsevier B.V. Published by Elsevier Inc. All rights reserved.
