Abeta43 is more frequent than Abeta40 in amyloid plaque cores from Alzheimer disease brains

J Neurochem. 2009 Jul;110(2):697-706. doi: 10.1111/j.1471-4159.2009.06170.x. Epub 2009 May 15.


One hallmark of Alzheimer disease (AD) is the extracellular deposition of the amyloid beta-peptide (Abeta) in senile plaques. Two major forms of Abeta are produced, 40 (Abeta40) and 42 (Abeta42) residues long. The most abundant form of Abeta is Abeta40, while Abeta42 is more hydrophobic and more prone to form toxic oligomers and the species of particular importance in early plaque formation. Thus, the length of the hydrophobic C-terminal seems to be very important for the oligomerization and neurotoxicity of the Abeta peptide. Here we investigated which Abeta species are deposited in AD brain. We analyzed plaque cores, prepared from occipital and frontal cortex, from sporadic and familial AD cases and performed a quantitative study using Abeta standard peptides. Cyanogen bromide was used to generate C-terminal Abeta fragments, which were analyzed by HPLC coupled to an electrospray ionisation ion trap mass spectrometer. We found a longer peptide, Abeta43, to be more frequent than Abeta40. No variants longer than Abeta43 could be observed in any of the brains. Immunohistochemistry was performed and was found to be in line with our findings. Abeta1-43 polymerizes rapidly and we suggest that this variant may be of importance for AD.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Alzheimer Disease / genetics
  • Alzheimer Disease / metabolism*
  • Alzheimer Disease / pathology
  • Amyloid beta-Peptides / biosynthesis
  • Amyloid beta-Peptides / genetics
  • Amyloid beta-Peptides / metabolism*
  • Brain Chemistry* / genetics
  • Female
  • Genetic Variation
  • Humans
  • Male
  • Middle Aged
  • Peptide Fragments / biosynthesis
  • Peptide Fragments / genetics
  • Peptide Fragments / metabolism*
  • Plaque, Amyloid / chemistry*
  • Plaque, Amyloid / metabolism*
  • Plaque, Amyloid / pathology


  • Amyloid beta-Peptides
  • Peptide Fragments
  • amyloid beta-protein (1-40)
  • amyloid beta-protein (1-43)