Biochemical detection of Aβ isoforms: Implications for pathogenesis, diagnosis, and treatment of Alzheimer's disease

Todd E. Golde, Christopher B. Eckman, Steven G. Younkin

Research output: Contribution to journalReview article

242 Scopus citations

Abstract

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 ~4 kDa amyloid β-peptide (Aβ) 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 Aβ together with genetic studies of AD have all supported the hypothesis that altered Aβ metabolism leading to aggregation plays a causal role in AD. Although there remains controversy as to whether Aβ 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 Aβ in AD pathogenesis, many important aspects of Aβ biology remain a mystery. This review will highlight those aspects of Aβ biology that have led to our increased understanding of the pathogenesis of AD as well as areas which warrant additional study. Copyright (C) 2000 Elsevier Science B.V.

Original languageEnglish (US)
Pages (from-to)172-187
Number of pages16
JournalBiochimica et Biophysica Acta - Molecular Basis of Disease
Volume1502
Issue number1
DOIs
StatePublished - Jul 26 2000

Keywords

  • Alzheimer's disease
  • Amyloid β protein precursor
  • Biomarker
  • ELISA
  • Protease

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology

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