title: Metabolism of amyloid β peptide and pathogenesis of Alzheimer's disease.
abstract: The conversion of what has been interpreted as "normal brain aging" to Alzheimer's disease (AD) via transition states, i.e., preclinical AD and mild cognitive impairment, appears to be a continuous process caused primarily by aging-dependent accumulation of amyloid β peptide (Aβ) in the brain. This notion however gives us a hope that, by manipulating the Aβ 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. Aβ is constantly produced from its precursor and immediately catabolized under normal conditions, whereas dysmetabolism of Aβ seems to lead to pathological deposition upon aging. We have focused our attention on elucidation of the unresolved mechanism of Aβ catabolism in the brain. In this review, I describe a new approach to prevent AD development by reducing Aβ burdens in aging brains through up-regulation of the catabolic mechanism involving neprilysin that can degrade both monomeric and oligomeric forms of Aβ. The strategy of combining presymptomatic diagnosis with preventive medicine seems to be the most pragmatic in both medical and socioeconomical terms.(Communicated by Kunihiko SUZUKI, M.J.A.).
authors.affiliation: Laboratory for Proteolytic Neuroscience, RIKEN Brain Science Institute, Saitama, Japan. saido@brain.riken.jp
authors.forename: Takaomi C
authors.initials: TC
authors.lastname: Saido
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy / Q000209:etiology* / Q000378:metabolism* / Q000473:pathology; D000595:Amino Acid Sequence; D016229:Amyloid beta-Peptides / Q000737:chemistry / Q000378:metabolism*; D000818:Animals; D004338:Drug Combinations; D004359:Drug Therapy, Combination; D006801:Humans; D008969:Molecular Sequence Data; D059748:Proteolysis / Q000187:drug effects
chemical_list: D016229:Amyloid beta-Peptides; D004338:Drug Combinations