Amyloid-beta and tau peptides (Aβ and Tau)

Amyloid-beta (Aβ) and tau are the hallmark proteins of Alzheimer's disease (AD) pathology (PubMed: 33358381). Aβ is a peptide fragment (typically 37–43 amino acids) produced by the sequential cleavage of the amyloid precursor protein (APP) by β-secretase (BACE1) and γ-secretase (UniProt: P05067). It aggregates into extracellular plaques, which are thought to initiate a cascade of neurotoxicity and synaptic dysfunction. Tau is a microtubule-associated protein (MAPT) that normally stabilizes axonal microtubules; however, in AD, it becomes hyperphosphorylated and forms intracellular neurofibrillary tangles (UniProt: P10636). Therapeutic interventions targeting Aβ, such as the monoclonal antibodies lecanemab and donanemab, aim to reduce plaque burden and have shown efficacy in slowing cognitive decline in early-stage patients (FDA: Leqembi, Kisunla). Tau-targeted therapies, including antibodies like bepranemab, focus on preventing the trans-synaptic spread of tau pathology, which correlates more closely with clinical symptoms than amyloid deposition (PubMed: 35115370).

Other names

Amyloid betaAbetaAβTau proteinMicrotubule-associated protein tauMAPTAmyloid-β proteinNeurofibrillary tanglesAmyloid plaquesAβ42p-tau

The primary mechanisms of action include monoclonal antibody-mediated clearance of protein aggregates via microglial phagocytosis, inhibition of peptide aggregation into toxic oligomers, and stabilization of microtubules to prevent tau dissociation (PubMed: 33358381, 35115370).