N-terminal pyroglutamate-modified amyloid beta (pGlu-Aβ) (pGlu-Aβ)

N-terminal pyroglutamate-modified amyloid beta (pGlu-Aβ) is a highly pathogenic and truncated form of the amyloid beta peptide, characterized by the conversion of an N-terminal glutamate residue at position 3 into pyroglutamate (Saido et al., 1995, Neuron). This post-translational modification, catalyzed by the enzyme glutaminyl cyclase, significantly increases the peptide's hydrophobicity and resistance to enzymatic degradation, leading to rapid aggregation into neurotoxic oligomers and stable amyloid plaques (Schilling et al., 2004, Biological Chemistry). Unlike standard amyloid beta, pGlu-Aβ is predominantly found within deposited plaques rather than in soluble monomeric forms, making it a highly specific target for immunotherapy (Mintun et al., 2021, NEJM). Drugs like donanemab are designed to recognize this specific epitope, triggering the immune system to clear existing plaque burdens from the brain (Sims et al., 2023, JAMA). By targeting the seeded core of plaques, these therapies aim to slow the clinical progression of Alzheimer's disease. The presence of pGlu-Aβ is strongly associated with the severity of cognitive decline and neurodegeneration in affected patients (Cynis et al., 2009, Molecular Neurodegeneration).

Other names

AβpE3Pyroglutamate-3 amyloid betapE3-AβN3pE-AβPyroglutamyl amyloid beta peptide

Monoclonal antibody-mediated clearance of amyloid plaques via microglial phagocytosis.