Small assemblies of unmodified amyloid β-protein are the proximate neurotoxin in Alzheimer's disease

W. L. Klein, W. B. Stine, D. B. Teplow*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

432 Scopus citations


Pioneering work in the 1950s by Christian Anfinsen on the folding of ribonuclease has shown that the primary structure of a protein "encodes" all of the information necessary for a nascent polypeptide to fold into its native, physiologically active, three-dimensional conformation (for his classic review, see [Science 181 (1973) 223]). In Alzheimer's disease (AD), the amyloid β-protein (Aβ) appears to play a seminal role in neuronal injury and death. Recent data have suggested that the proximate effectors of neurotoxicity are oligomeric Aβ assemblies. A fundamental question, of relevance both to the development of therapeutic strategies for AD and to understanding basic laws of protein folding, is how Aβ assembly state correlates with biological activity. Evidence suggests, as argued by Anfinsen, that the formation of toxic Aβ structures is an intrinsic feature of the peptide's amino acid sequence - one requiring no post-translational modification or invocation of peptide-associated enzymatic activity.

Original languageEnglish (US)
Pages (from-to)569-580
Number of pages12
JournalNeurobiology of Aging
Issue number5
StatePublished - 2004


  • ADDLs
  • Alzheimer's disease
  • Amyloid
  • Amyloid β-protein
  • Neurotoxicity
  • Oligomers
  • Paranucleus
  • Protofibril

ASJC Scopus subject areas

  • Clinical Neurology
  • Geriatrics and Gerontology
  • Aging
  • General Neuroscience
  • Developmental Biology


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