TIPS review
Amyloid deposition as the central event in the aetiology of Alzheimer's disease

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Abstract

While there may be many causes of Alzheimer's disease (AD), the same pathological sequence of events, described here by John Hardy and David Allsop, is likely to occur in all cases. The recent discovery of a pathogenic mutation in the β-amyloid precursor protein (APP) gene on chromosome 21 suggests that APP mismetabolism and β-amyloid deposition are the primary events in the disease process. The occurrence of AD in Down syndrome is consistent with this hypothesis. The pathological cascade for the disease process is most likely to be: β-amyloid deposition → tau phosphorylation and tangle formation → neuronal death. The development of a biochemical understanding of this pathological cascade will facilitate rational design of drugs to intervene in this process.

References (50)

  • H. Yamaguchi et al.

    Brain Res.

    (1990)
  • O. Bugiani et al.

    Neurosci. Lett.

    (1989)
  • H. Yamaguchi

    Brain Res.

    (1990)
  • H. Braak et al.

    Neurosci. Lett.

    (1986)
  • Y. Ihara

    Brain Res.

    (1988)
  • P.H. St George-Hyslop

    Neurobiol. Aging

    (1989)
  • A. Weidemann

    Cell

    (1989)
  • M.B. Podlisny

    Biochem. Biophys. Res. Commun.

    (1990)
  • G.M. Cole et al.

    Biochem. Biophys. Res. Commun.

    (1990)
  • A.I. Bush

    J. Biol. Chem.

    (1990)
  • M. Chen et al.

    Neurosci. Lett.

    (1991)
  • D. Allsop et al.

    Brain Res.

    (1991)
  • M. Shoji

    Brain Res.

    (1990)
  • D.M.A. Mann et al.

    J. Neurol. Sci.

    (1990)
  • J.S. Whitson et al.

    Neurosci. Lett.

    (1990)
  • C.L. Masters
  • G.G. Glenner et al.

    Biochem. Biophys. Res. Commun.

    (1984)
  • J. Kang

    Nature

    (1987)
  • N. Kitaguchi et al.

    Nature

    (1988)
  • D.M.A. Mann

    Neuropathol. Appl. Neurobiol.

    (1989)
  • B. Rumble

    New Engl. J. Med.

    (1989)
  • G.W. Roberts et al.

    J. Neurol. Neurosurg. Psychiat.

    (1990)
  • K. Ogomori

    Am. J. Pathol.

    (1989)
  • M. Kidd

    Nature

    (1963)
  • R.A. Crowther

    Biochim. Biophys. Acta

    (1991)
  • Cited by (1990)

    View all citing articles on Scopus
    View full text