Amyloid beta peptide N-terminal residues 1-5 (Aβ1-5)

The N-terminal residues 1–5 of the amyloid beta (Aβ) peptide, characterized by the amino acid sequence DAEFR, constitute a critical epitope for therapeutic intervention in Alzheimer's disease [1.3.1, 1.3.2]. This region is highly solvent-exposed in both soluble oligomers and insoluble fibrils of the major Aβ isoforms, Aβ1–40 and Aβ1–42, making it an ideal target for monoclonal antibodies and vaccines [1.3.3, 1.5.3]. Biologically, the N-terminus plays a role in modulating the aggregation propensity of Aβ and stabilizing the structural fold of mature fibrils through interfilament contacts [1.4.1]. In the context of disease, the accumulation of Aβ into neurotoxic species is a hallmark of Alzheimer's pathology and cerebral amyloid angiopathy [1.1.2, 1.4.3]. Drugs targeting this specific 1–5 sequence, such as the monoclonal antibody bapineuzumab, aim to reduce amyloid burden by promoting microglial-mediated clearance and preventing further aggregation [1.3.5, 1.5.2]. However, therapeutic efforts have been complicated by safety concerns like amyloid-related imaging abnormalities (ARIA) and the need for early intervention to achieve clinical efficacy [1.2.1, 1.2.3].

Other names

DAEFR epitopeN-terminal amyloid beta epitopeAβ(1-5)Amyloid beta 1-5

Passive and active immunotherapy targeting the N-terminus of amyloid beta to promote clearance of plaques and soluble oligomers, inhibit fibril formation, and neutralize neurotoxicity [1.3.2, 1.5.2].