Aβ43 is more frequent than Aβ40 in amyloid plaque cores from Alzheimer disease brains

One hallmark of Alzheimer disease (AD) is the extracellular deposition of the amyloid beta-peptide (A beta) in senile plaques. Two major forms of A beta are produced, 40 (A beta 40) and 42 (A beta 42) residues long. The most abundant form of A beta is A beta 40, while A beta 42 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 A beta peptide. Here we investigated which A beta 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 A beta standard peptides. Cyanogen bromide was used to generate C-terminal A beta fragments, which were analyzed by HPLC coupled to an electrospray ionisation ion trap mass spectrometer. We found a longer peptide, A beta 43, to be more frequent than A beta 40. No variants longer than A beta 43 could be observed in any of the brains. Immunohistochemistry was performed and was found to be in line with our findings. A beta 1-43 polymerizes rapidly and we suggest that this variant may be of importance for AD.