Antibody against Small Aggregated Peptide Specifically Recognizes Toxic Aβ-42 Oligomers in Alzheimer's Disease

Riddhi U. Bodani, Urmi Sengupta, Diana L. Castillo-Carranza, Marcos J. Guerrero-Muñoz, Julia E. Gerson, Jai Rudra, Rakez Kayed

Research output: Contribution to journalArticle

12 Scopus citations

Abstract

Amyloid-beta (Aβ) oligomers have emerged as the most toxic species in Alzheimer's disease (AD) and other amyloid pathologies. Also, Aβ-42 peptide is more aggregation-prone compared to other Aβ isoforms. Thus, we synthesized a small peptide of repeated sequence containing the last three amino acids, Val-40, Ile-41, and Ala-42 of Aβ-42 that was subsequently aggregated and used to generate a novel antibody, VIA. In this study, we examined human AD and Tg2576 mouse brain samples using VIA in combination with other amyloid-specific antibodies and confirmed the specificity of VIA to oligomeric Aβ-42. Moreover, we found that VIA does not recognize classic amyloid plaques composed of fibrillar Aβ or Aβ-40 ex vivo. Since VIA recognizes a distinct epitope specific to Aβ-42 oligomers, it may have broad use for examining the accumulation of these oligomers in AD and other neurodegenerative diseases. VIA may also be used in immunotherapy studies to prevent neurodegenerative effects associated with Aβ-42 oligomers.

Original languageEnglish (US)
Pages (from-to)1981-1989
Number of pages9
JournalACS Chemical Neuroscience
Volume6
Issue number12
DOIs
StatePublished - Dec 16 2015

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Keywords

  • Amyloid oligomers
  • repeated sequence
  • small peptide

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Physiology
  • Cognitive Neuroscience

Cite this

Bodani, R. U., Sengupta, U., Castillo-Carranza, D. L., Guerrero-Muñoz, M. J., Gerson, J. E., Rudra, J., & Kayed, R. (2015). Antibody against Small Aggregated Peptide Specifically Recognizes Toxic Aβ-42 Oligomers in Alzheimer's Disease. ACS Chemical Neuroscience, 6(12), 1981-1989. https://doi.org/10.1021/acschemneuro.5b00231