Toxicity of pyroglutaminated amyloid β-peptides 3(pE)-40 and -42 is similar to that of Aβ1 -40 and -42

T. L. Tekirian, A. Y. Yang, C. Glabe, J. W. Geddes

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49 Scopus citations


An N-terminal truncated isoform of the amyloid β-peptide (Aβ) that begins with a pyroglutamate (pE) residue at position 3 [Aβ3(pE)-42] is the predominant isoform found in senile plaques. Based upon previous in vitro studies regarding Aβ N-terminal truncated isoforms, it has been hypothesized that Aβ3(pE)-x isoforms may aggregate more rapidly and become more toxic than corresponding Aβ1-x peptides. However, the toxicity and aggregation properties of Aβ3(pE)-42 and Aβ3(pE)-40 have not previously been examined. After initial solubilization and 1-week preaggregation of each peptide at 37°C and pH 7.4, the toxicity of 5-50 μM Aβ3(pE)-42 was similar to that of Aβ1-42. Moreover, the toxicity of Aβ3(pE)-40 paralleled that reduced by Aβ1-40 in both 1 day in vitro (DIV) cortical and 7 DIV hippocampal cells. Circular dichroism spectra did not reveal major differences in secondary structure between aged Aβ1-42, Aβ3(pE)-42, Aβ3(pE)-40, and Aβ1-40 or freshly solubilized forms of these peptides. Overall, the data indicate that the loss of the two N-terminal amino acids and the cyclization of glutamate at position 3 do not alter the extracellular toxicity of Aβ.

Original languageEnglish
Pages (from-to)1584-1589
Number of pages6
JournalJournal of Neurochemistry
Issue number4
StatePublished - 1999


  • Alzheimer's disease
  • Amyloid β-peptide
  • Circular dichroism
  • Neurotoxins
  • Peptide fragments

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience


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