Pyro-Glu modified beta-Amyloid forms show higher toxicity
Sequential proteolytic cleavage of the Amyloid Precursor Protein (APP) by secretases (α, β, γ) generates beta-Amyloid peptide fragments. Beta-Amyloid 1-42 forms a major component of amyloid plaques in neurons of Alzheimer’s disease (AD) brains, while beta-Amyloid 1-40 is taken as a negative control of beta-Amyloid 1-42 in most studies.
N-terminally truncated beta-Amyloid 3-40 ad 11-40, both having a Glu as first residue, are subjected to pyro-glutamination. Pyroglutamate-modified (Pyr) beta-Amyloid 3-40 and 11-40 have been described as major compounds in the senile AD plaques. Pyro-Glu modified beta-Amyloid forms are more resistant to degradation, show higher toxicity and have increased aggregation propensity compared to the non-modified beta-Amyloid equivalent.