Quantitative mass spectrometric assay of N-terminally truncated and pyroglutamylated amyloid beta peptides in human brain with Alzheimer’s disease

N-terminally truncated, pyroglutamylated (pE) forms of amyloid beta peptides (Aβs) are strongly associated with Alzheimer’s disease (AD) and have been proposed as initiators of AD pathogenesis. pE-Aβs contain an N-terminal pyroglutamate, whose modification from glutamate is catalyzed by glutaminyl cyclase (QC). pE-Aβs are believed to be more cytotoxic and tend to aggregate more rapidly than conventional Aβs, while QC activity and pE-Aβ levels have been observed to be increased several-fold in AD brain.