Oligomerization and toxicity of β-amyloid-42 implicated in Alzheimer's disease

Omar M.A. El-Agnaf, Devinder S. Mahil, Bhroma P. Patel, Brian M. Austen

Research output: Contribution to journalArticlepeer-review

169 Citations (Scopus)

Abstract

β-Amyloid protein (Aβ) is the major component of senile plaques found in the brains of Alzheimer's patients. A novel ELISA has been developed which probes the early stages of oligomerization of Aβ. Incubation of Aβ solutions at 37°C and pH 7.4 produces soluble oligomers in a concentration- dependent manner. Fresh Aβ42 solutions rapidly form soluble oligomers, whereas Aβ40 solutions require prolonged incubation to produce oligomers. Fresh Aβ42 solutions are more toxic to human neuroblastoma SH-SY5Y cells than Aβ40 solutions, possibly mediated by soluble oligomers. The differences between Aβ42 and Aβ40 could explain the association of the longer form with familial early-onset Alzheimer's disease. We also report a new strategy for solid-phase synthesis of Aβ peptides which gives high yield and purity of the initial crude preparation.

Original languageEnglish
Pages (from-to)1003-1007
Number of pages5
JournalBiochemical and Biophysical Research Communications
Volume273
Issue number3
DOIs
Publication statusPublished - Jul 14 2000
Externally publishedYes

Keywords

  • Aggregation
  • Alzheimer's disease
  • Amyloid
  • Oligomerization
  • Solid-phase peptide synthesis
  • Toxicity

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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