Pyroglutamate-modified amyloid-beta peptide (specifically Aβ 3-42 with pyroglutamate at position 3) (Aβ pE3-42)

Pyroglutamate-modified amyloid-beta peptide (Aβ pE3-42) is an N-terminally truncated product of amyloid precursor protein (APP) proteolysis, in which the third amino acid’s glutamate is cyclized via glutaminyl cyclase to form a pyroglutamate residue. This modification increases the peptide’s hydrophobicity, resistance to proteolytic degradation, and aggregation propensity, enabling Aβ pE3-42 to assemble efficiently into oligomers and fibrillar plaques. These aggregates are highly neurotoxic, induce synaptic and cellular dysfunction, and are a prominent and early component of amyloid plaques in Alzheimer’s disease brains. Due to these pathogenic properties and their abundance in plaques, Aβ pE3-42 is considered a structurally and functionally distinct species—and an important therapeutic and diagnostic target for disease-modifying interventions in Alzheimer’s disease

Other names

Pyroglutamate amyloid-beta 3-42Aβ pE3-42Pyroglutamate-modified AβAβN3(pE)pE-Aβ(3–42)

Antibody-mediated clearance of Aβ pE3-42 from plaques. Inhibition of glutaminyl cyclase to block pyroglutamate formation. Disruption or neutralization of Aβ pE3-42 oligomerization and seeding.