Metabolism of amyloid beta peptide and pathogenesis of Alzheimer's disease. Towards presymptomatic diagnosis, prevention and therapy

Neurosci Res. 2006 Apr;54(4):235-53. doi: 10.1016/j.neures.2005.12.015. Epub 2006 Feb 2.

Abstract

The conversion of what has been interpreted as "normal brain aging" to Alzheimer's disease (AD) via a transition state, i.e. mild cognitive impairment, appears to be a continuous process caused primarily by aging-dependent accumulation of amyloid beta peptide (Abeta) in the brain. This notion give us a hope that, by manipulating the Abeta levels in the brain, we may be able not only to prevent and cure the disease but also to partially control some very significant aspects of brain aging. Abeta is constantly produced from its precursor and immediately catabolized under normal conditions, whereas dysmetabolism of Abeta seems to lead to pathological deposition upon aging. We have focused our attention on elucidation of the unresolved mechanism of Abeta catabolism in the brain. In this review, we describe a new approach to prevent AD development by reducing Abeta burdens in aging brains through up-regulation the catabolic mechanism involving neprilysin that can degrade both monomeric and oligomeric forms of Abeta. The strategy of combining presymptomatic diagnosis with preventive medicine seems to be the most pragmatic in both medical and socio-economical terms. We also introduce a novel non-invasive amyloid imaging approach using a high-power magnetic resonance imaging (MRI) for the presymptomatic diagnosis of AD.

Publication types

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

MeSH terms

  • Alzheimer Disease* / diagnosis
  • Alzheimer Disease* / prevention & control
  • Alzheimer Disease* / therapy
  • Amyloid beta-Peptides / metabolism*
  • Animals
  • Disease Models, Animal
  • Humans

Substances

  • Amyloid beta-Peptides