Biochemical detection of Abeta isoforms: implications for pathogenesis, diagnosis, and treatment of Alzheimer's disease

Biochim Biophys Acta. 2000 Jul 26;1502(1):172-87. doi: 10.1016/s0925-4439(00)00043-0.


Prior to the identification of the various abnormal proteins deposited as fibrillar aggregates in the Alzheimer's disease (AD) brain, there was tremendous controversy over the importance of the various lesions with respect to primacy in the pathology of AD. Nevertheless, based on analogy to systemic amyloidosis, many investigators believed that the amyloid deposits in AD played a causal role and that characterization of these deposits would hold the key to understanding this complex disease. Indeed, in retrospect, it was the initial biochemical purifications of the approximately 4 kDa amyloid beta-peptide (Abeta) from amyloid deposits in the mid 1980s that launched a new era of AD research (Glenner and Wong, Biochem. Biophys. Res. Commun. 122 (1984) 1121-1135; Wong et al., Proc. Natl. Acad Sci. USA 82 (1985) 8729 8732; and Masters et al., Proc. Natl. Acad Sci. USA 82 (1985) 4245-4249). Subsequent studies of the biology of Abeta together with genetic studies of AD have all supported the hypothesis that altered Abeta metabolism leading to aggregation plays a causal role in AD. Although there remains controversy as to whether Abeta deposited as classic amyloid or a smaller, aggregated, form causes AD, the relevance of studying the amyloid deposits has certainly been proven. Despite the significant advances in our understanding of the role of Abeta in AD pathogenesis, many important aspects of Abeta biology remain a mystery. This review will highlight those aspects of Abeta biology that have led to our increased understanding of the pathogenesis of AD as well as areas which warrant additional study.

Publication types

  • Comparative Study
  • Review

MeSH terms

  • Alzheimer Disease / diagnosis
  • Alzheimer Disease / etiology*
  • Alzheimer Disease / therapy
  • Amino Acid Sequence
  • Amyloid beta-Peptides / analysis*
  • Amyloid beta-Peptides / genetics
  • Amyloid beta-Peptides / metabolism
  • Animals
  • Biomarkers / analysis
  • Brain / metabolism*
  • Brain Chemistry*
  • Cell Line
  • Electrophoresis, Polyacrylamide Gel
  • Enzyme-Linked Immunosorbent Assay
  • Humans
  • Mass Spectrometry
  • Membrane Proteins / analysis
  • Membrane Proteins / genetics
  • Molecular Sequence Data
  • Mutation
  • Peptide Fragments / analysis
  • Peptide Fragments / genetics
  • Presenilin-1
  • Presenilin-2
  • Protein Isoforms / analysis


  • Amyloid beta-Peptides
  • Biomarkers
  • Membrane Proteins
  • PSEN1 protein, human
  • PSEN2 protein, human
  • Peptide Fragments
  • Presenilin-1
  • Presenilin-2
  • Protein Isoforms
  • amyloid beta-protein (1-42)