Anti-oligomeric Aβ Single-chain Variable Domain Antibody Blocks Aβ-induced Toxicity Against Human Neuroblastoma Cells

Andleeb Zameer, Srinath Kasturirangan, Sharareh Emadi, Sridevi V. Nimmagadda, Michael Sierks

Research output: Contribution to journalArticle

59 Citations (Scopus)

Abstract

The Amyloid-β (Aβ) peptide is a major component of the amyloid plaques associated with Alzheimer's disease (AD). Recent studies suggest that the most toxic forms of Aβ are small, soluble oligomeric aggregates. Here, we report the isolation and characterization of a single-chain variable domain (scFv) antibody isolated against oligomeric Aβ using a protocol developed in our laboratory that combines phage display technology and atomic force microscopy (AFM). Starting with a randomized, single framework phage display library, after three rounds of selection against oligomeric Aβ, we identified an scFv that bound oligomeric Aβ specifically, but not monomeric or fibrillar forms. The anti-oligomeric scFv inhibits Aβ aggregation and toxicity, and reduces the toxicity of preformed oligomeric Aβ towards human neuroblastoma cells. When used to probe samples of human brain tissue, the scFv reacted with AD tissue but not a healthy control or Parkinson's disease brain samples. The anti-oligomeric Aβ scFv therefore has potential therapeutic and diagnostic applications in specifically targeting or identifying the toxic morphologies of Aβ in AD brains.

Original languageEnglish (US)
Pages (from-to)917-928
Number of pages12
JournalJournal of Molecular Biology
Volume384
Issue number4
DOIs
StatePublished - Dec 26 2008

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Neuroblastoma
Alzheimer Disease
Poisons
Bacteriophages
Antibodies
Brain
Single-Chain Antibodies
Atomic Force Microscopy
Amyloid Plaques
Amyloid
Libraries
Parkinson Disease
Technology
Peptides
Therapeutics

Keywords

  • Alzheimer's disease
  • oligomers
  • phage display
  • ScFv

ASJC Scopus subject areas

  • Molecular Biology

Cite this

Anti-oligomeric Aβ Single-chain Variable Domain Antibody Blocks Aβ-induced Toxicity Against Human Neuroblastoma Cells. / Zameer, Andleeb; Kasturirangan, Srinath; Emadi, Sharareh; Nimmagadda, Sridevi V.; Sierks, Michael.

In: Journal of Molecular Biology, Vol. 384, No. 4, 26.12.2008, p. 917-928.

Research output: Contribution to journalArticle

Zameer, Andleeb ; Kasturirangan, Srinath ; Emadi, Sharareh ; Nimmagadda, Sridevi V. ; Sierks, Michael. / Anti-oligomeric Aβ Single-chain Variable Domain Antibody Blocks Aβ-induced Toxicity Against Human Neuroblastoma Cells. In: Journal of Molecular Biology. 2008 ; Vol. 384, No. 4. pp. 917-928.
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