N-terminal truncated pyroglutamate-modified amyloid-beta aggregate (Aβ pE3-42 (for the most studied form); more generally, pyroglutamate Aβ or pE-Aβ)

N-terminal truncated pyroglutamate-modified amyloid-beta aggregates are a pathological protein species formed when the amyloid-beta (Aβ) peptide—normally produced by enzymatic cleavage of amyloid precursor protein in neurons—is truncated at its N-terminus, exposing a glutamate residue at position 3 or 11. This residue undergoes cyclization, catalyzed by the enzyme glutaminyl cyclase, to form a pyroglutamate N-terminus[1][9]. The resulting pyroglutamate-modified Aβ (especially Aβ pE3-42) is highly aggregation-prone, forms particularly stable oligomers and fibrils, and constitutes a substantial proportion of amyloid plaques in Alzheimer’s disease brains[1][5][7][9]. These aggregates are more hydrophobic, more resistant to proteolytic degradation, and have increased neurotoxicity compared to unmodified Aβ, making them a focus of AD pathogenesis research and a promising therapeutic target. Specific immunotherapies and enzyme inhibitors targeting this form of Aβ are in development to reduce pathological load and functional decline in Alzheimer’s disease[5][7].

Other names

Pyroglutamate amyloid-betaPyroglutamate-modified amyloid-betapE3-Aβ (or Aβ pE3-42, indicating truncation at position 3)N-terminal truncated AβpE-Aβ aggregatesN3pE AβPyroglutamylated amyloid-beta

Binding and clearance of pyroglutamate-modified Aβ by antibodies Inhibition of glutaminyl cyclase to reduce formation of pyroglutamate-modified Aβ Promotion of immune-mediated clearance of aggregates