Amyloid-beta protein 42 (Aβ42) (Aβ42)

Amyloid-beta 42 (Aβ42) is a 42-amino acid peptide derived from the proteolytic cleavage of the amyloid precursor protein (APP) by β-secretase and γ-secretase (UniProt P05067). In its misfolded monomeric state, Aβ42 is highly prone to self-aggregation due to its hydrophobic C-terminus, leading to the formation of neurotoxic oligomers and insoluble amyloid plaques (PubMed: 28913148). This process is a hallmark of Alzheimer's disease pathogenesis, as described by the amyloid cascade hypothesis (PubMed: 30635407). Therapeutic interventions targeting misfolded Aβ42 monomers, such as the monoclonal antibody solanezumab, aim to sequester these species and prevent their assembly into larger, more toxic aggregates (PubMed: 29361447). While some drugs target the monomeric form to enhance clearance, others focus on the transition from monomer to oligomer to mitigate synaptic dysfunction and neurodegeneration (PubMed: 31034602). Monitoring the Aβ42/Aβ40 ratio in cerebrospinal fluid and plasma serves as a critical biomarker for early diagnosis and therapeutic efficacy (PubMed: 30670666). Despite the focus on pathological forms, physiological Aβ may play roles in synaptic modulation and antimicrobial defense, raising concerns about total depletion (PubMed: 27225120). Overall, Aβ42 monomers represent a key upstream target in the complex landscape of neurodegenerative proteinopathies.

Other names

Amyloid-beta 1-42Abeta 42Aβ1-42Beta-amyloid 42Misfolded Aβ42 monomerSoluble Aβ42

Therapeutic agents target misfolded Aβ42 monomers through 'peripheral sink' mechanisms or direct conformational stabilization to prevent the nucleation and elongation of toxic amyloid fibrils (PubMed: 29361447, PubMed: 31034602).