Aβ deposition inhibitor screen using synthetic amyloid

William P. Esler, Evelyn R. Stimson, Joseph R. Ghilardi, Arthur M. Felix, Yi An Lu, Harry V. Vinters, Patrick W. Mantyh, John E. Maggio

Research output: Contribution to journalArticle

80 Scopus citations

Abstract

The formation, growth, and maturation of brain amyloid “senile” plaques are essential pathological processes in Alzheimer’s disease (AD) and key targets for therapeutic intervention. The process of in vitro deposition of Aβ at physiological concentrations onto plaques in AD brain preparations has been well characterized, but is cumbersome for drug discovery. We describe here a high-throughput screen for inhibitors of Aβ deposition onto a synthetic template (synthaloid) of fibrillar Aβ immobilized in a polymer matrix. Synthaloid is indistinguishable from plaques in AD brain (the natural template) in deposition kinetics, pH profile, and structure-activity relationships for both Aβ analogs and inhibitors. Synthaloid, in contrast to current Aβ aggregation screens, accurately predicted inhibitor potency for Aβ deposition onto AD cortex preparations, validating its use in searching for agents that can slow the progression of AD and exposing a previously inaccessible target for drug discovery.

Original languageEnglish (US)
Pages (from-to)258-263
Number of pages6
JournalNature biotechnology
Volume15
Issue number3
DOIs
StatePublished - Mar 1997
Externally publishedYes

Keywords

  • Alzheimer’s disease
  • Aβ deposition
  • Congo red
  • High-thoughput screen
  • Structure-activity

ASJC Scopus subject areas

  • Biotechnology
  • Bioengineering
  • Applied Microbiology and Biotechnology
  • Molecular Medicine
  • Biomedical Engineering

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  • Cite this

    Esler, W. P., Stimson, E. R., Ghilardi, J. R., Felix, A. M., Lu, Y. A., Vinters, H. V., Mantyh, P. W., & Maggio, J. E. (1997). Aβ deposition inhibitor screen using synthetic amyloid. Nature biotechnology, 15(3), 258-263. https://doi.org/10.1038/nbt0397-258