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

Research output: Contribution to journalArticle

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Abstract

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
Volume282
Issue number31
DOIs
StatePublished - Aug 3 2007

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Poisons
Oligomers
Amyloid
Alzheimer Disease
Antibodies
Vaccination
Preexisting Condition Coverage
Epitopes
Therapeutics
Vaccines
Pathology
Cytotoxicity
Conformations
Peptides
Brain
Agglomeration

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Anti-Aβ1-11 antibody binds to different β-amyloid species, inhibits fibril formation, and disaggregates preformed fibrils but not the most toxic oligomers. / Mamikonyan, Grigor; Necula, Mihaela; Mkrtichyan, Mikayel; Ghochikyan, Anahit; Petrushina, Irina; Movsesyan, Nina; Mina, Erene; Kiyatkin, Anatoly; Glabe, Charles G.; Cribbs, David H.; Agadjanyan, Michael G.

In: Journal of Biological Chemistry, Vol. 282, No. 31, 03.08.2007, p. 22376-22386.

Research output: Contribution to journalArticle

Mamikonyan, G, Necula, M, Mkrtichyan, M, Ghochikyan, A, Petrushina, I, Movsesyan, N, Mina, E, Kiyatkin, A, Glabe, CG, Cribbs, DH & Agadjanyan, MG 2007, 'Anti-Aβ1-11 antibody binds to different β-amyloid species, inhibits fibril formation, and disaggregates preformed fibrils but not the most toxic oligomers', Journal of Biological Chemistry, vol. 282, no. 31, pp. 22376-22386. https://doi.org/10.1074/jbc.M700088200
Mamikonyan, Grigor ; Necula, Mihaela ; Mkrtichyan, Mikayel ; Ghochikyan, Anahit ; Petrushina, Irina ; Movsesyan, Nina ; Mina, Erene ; Kiyatkin, Anatoly ; Glabe, Charles G. ; Cribbs, David H. ; Agadjanyan, Michael G. / Anti-Aβ1-11 antibody binds to different β-amyloid species, inhibits fibril formation, and disaggregates preformed fibrils but not the most toxic oligomers. In: Journal of Biological Chemistry. 2007 ; Vol. 282, No. 31. pp. 22376-22386.
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