Aβ42 and Aβ40: similarities and differences

J Pept Sci. 2015 Jul;21(7):522-9. doi: 10.1002/psc.2789. Epub 2015 May 28.


The abnormal accumulation of amyloid-β (Aβ) peptide in the brain is one of the most important hallmarks of Alzheimer's disease. Aβ is an aggregation-prone and toxic polypeptide with 39-43 residues, derived from the amyloid precursor protein proteolysis process. According to the amyloid hypothesis, abnormal accumulation of Aβ in the brain is the primary influence driving Alzheimer's disease pathologies. Among all kinds of Aβ isoforms, Aβ40 and Aβ42 are believed to be the most important ones. Although these two kinds of Aβ differ only in two amino acid residues, recent studies show that they differ significantly in their metabolism, physiological functions, toxicities, and aggregation mechanism. In this review, we mainly summarize the similarities and differences between Aβ42 and Aβ40, recent studies on selective inhibitors as well as probes will also be mentioned.

Keywords: Aβ oligomers; Aβ40; Aβ42; aggregation mechanism; amyloid-β peptide.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Alzheimer Disease / metabolism*
  • Alzheimer Disease / pathology
  • Amino Acid Sequence
  • Amyloid beta-Peptides / antagonists & inhibitors
  • Amyloid beta-Peptides / chemistry*
  • Amyloid beta-Protein Precursor / chemistry*
  • Amyloid beta-Protein Precursor / metabolism
  • Antibodies, Monoclonal / biosynthesis
  • Antibodies, Monoclonal / chemistry
  • Brain Chemistry
  • Humans
  • Molecular Probes / chemistry
  • Molecular Sequence Data
  • Peptide Fragments / antagonists & inhibitors
  • Peptide Fragments / chemistry*
  • Protein Aggregation, Pathological / metabolism*
  • Protein Aggregation, Pathological / pathology
  • Protein Structure, Secondary
  • Proteolysis
  • Styrenes / chemistry
  • Thiazoles / chemistry


  • 1-iodo-2,5-bis-(3-hydroxycarbonyl-4-methoxy)styryl-benzene
  • 2-(4'-dimethylaminophenyl)-6-iodobenzothiazole
  • Amyloid beta-Peptides
  • Amyloid beta-Protein Precursor
  • Antibodies, Monoclonal
  • Molecular Probes
  • Peptide Fragments
  • Styrenes
  • Thiazoles
  • amyloid beta-protein (1-40)
  • amyloid beta-protein (1-42)