Anti-Aβ1-11 antibody binds to different β-amyloid species, inhibits fibril formation, and disaggregates preformed fibrils but not the most toxic oligomers

Grigor Mamikonyan, Mihaela Necula, Mikayel Mkrtichyan, Anahit Ghochikyan, Irina Petrushina, Nina Movsesyan, Erene Mina, Anatoly Kiyatkin, Charles G. Glabe, David H. Cribbs, Michael G. Agadjanyan

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85 Scopus citations


Different strategies proposed as therapy for Alzheimer disease (AD) have aimed to reduce the level of toxic forms of Aβ peptide in the brain. Here, we directly analyze the therapeutic utility of the polyclonal anti-Aβ1-11 antibody induced in 3xTg-AD mice vaccinated with the second generation prototype epitope vaccine. Substoichiometric concentrations of purified anti-Aβ1-11 antibody prevented aggregation of Aβ42 and induced disaggregation of preformed Aβ42 fibrils down to non-filamentous and nontoxic species. Anti-Aβ1-11 antibody delayed Aβ42 oligomer formation but ultimately appeared to stabilize nonfibrillar conformations, including oligomer-like assemblies. The reduced oligomer-mediated cytotoxicity observed upon preincubation of Aβ oligomers with the anti-Aβ 1-11 antibody in the absence of oligomer disaggregation suggests a possible oligomer rearrangement in the presence of the antibody. These in vitro observations suggest that preventive vaccination may protect from AD or may delay the onset of the disease, whereas therapeutic vaccination cannot disrupt the toxic oligomers and may only minimally alleviate preexisting AD pathology.

Original languageEnglish (US)
Pages (from-to)22376-22386
Number of pages11
JournalJournal of Biological Chemistry
Issue number31
Publication statusPublished - Aug 3 2007


ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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