Pyroglutamate Amyloid-β (Aβ): A Hatchet Man in Alzheimer Disease

Pyroglutamate-modified amyloid-β (Aβ(pE3)) peptides are gaining considerable attention as potential key participants in the pathology of Alzheimer disease (AD) due to their abundance in AD brain, high aggregation propensity, stability, and cellular toxicity. Transgenic mice that produce high levels of Aβ(pE3-42) show severe neuron loss. Recent in vitro and in vivo experiments have proven that the enzyme glutaminyl cyclase catalyzes the formation of Aβ(pE3). In this minireview, we summarize the current knowledge on Aβ(pE3), discussing its discovery, biochemical properties, molecular events determining formation, prevalence in the brains of AD patients, Alzheimer mouse models, and potential as a target for therapy and as a diagnostic marker.