Active Aβ vaccination fails to enhance amyloid clearance in a mouse model of Alzheimer's disease with Aβ42-driven pathology

Anna Nemirovsky, Jenny Shapiro, Rona Baron, Alex Kompaniets, Alon Monsonego

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

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.

Original languageEnglish
Pages (from-to)95-99
Number of pages5
JournalJournal of Neuroimmunology
Volume247
Issue number1-2
DOIs
StatePublished - 15 Jun 2012

Keywords

  • Alzheimer's disease
  • Amyloid beta-peptide
  • Aβ antibodies
  • Vaccine

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