Amyloid-beta peptide N-terminus (Aβ N-terminus)

The Amyloid-beta (Aβ) N-terminus refers to the initial sequence of amino acids (typically residues 1–15) of the Aβ peptide, generated by the cleavage of the Amyloid Precursor Protein (APP) by beta-secretase (BACE1) (UniProt P05067). This region is highly exposed in both soluble and insoluble forms of Aβ, making it a primary target for monoclonal antibodies in Alzheimer's disease therapy (Sevigny et al., 2016). Drugs like aducanumab and bapineuzumab bind to specific N-terminal epitopes to promote the clearance of amyloid plaques through microglial-mediated phagocytosis (Miles et al., 2013). Additionally, modifications such as the formation of pyroglutamate at the N-terminus (pGlu3-Aβ) create highly toxic and aggregation-prone species targeted by drugs like donanemab (Demattos et al., 2012). While these therapies aim to slow cognitive decline by reducing amyloid burden, they are frequently associated with Amyloid-Related Imaging Abnormalities (ARIA), which manifest as brain edema or microhemorrhage (Sperling et al., 2011). Consequently, the N-terminus remains a central focus for refining the efficacy and safety of anti-amyloid biologics.

Other names

Aβ N-terminal domainAmyloid-beta 1-xN-terminal Amyloid-beta epitopeAbeta N-terminus

Passive immunotherapy via monoclonal antibodies that bind N-terminal epitopes to facilitate microglial phagocytosis and plaque dissolution (Sevigny et al., 2016; Demattos et al., 2012).