N-terminal pyroglutamate-modified amyloid beta peptide (AβpE3)

N-terminal pyroglutamate-modified amyloid beta peptides (AβpE3) are truncated forms of the amyloid-β peptide in which the third N-terminal glutamate is post-translationally cyclized to form pyroglutamate, a reaction catalyzed mainly by glutaminyl cyclase. These peptides, especially AβpE3–42, are highly aggregation-prone, hydrophobic, neurotoxic, and form stable β-sheet-rich oligomers and fibrils that are resistant to degradation. AβpE3–42 constitutes a major component of amyloid plaques in brains affected by Alzheimer’s disease and serves as a pathological trigger by acting as a seed for further amyloid aggregation and neuronal damage. Their enhanced stability, aggregation, and protease resistance make them both a hallmark and a pathogenic driver in Alzheimer’s disease pathology, as well as a promising therapeutic target for drugs aiming to inhibit their formation or promote their clearance[2][4][5][7].

Other names

Pyroglutamate AβPyroglutamate amyloid-β3–42pEAβAβpE3-42AβN3(pE)Pyroglutamate-modified amyloid beta

Inhibition of enzymatic conversion to pyroglutamate form (e.g., QC inhibition reduces formation of AβpE3) Immunoneutralization and clearance by antibodies specific for AβpE3