title: Anti-amyloid activity of neprilysin in plaque-bearing mouse models of Alzheimer's disease.
abstract: Abnormally high concentrations of beta-amyloid peptide (Abeta) and amyloid plaque formation in Alzheimer's disease (AD) may be caused either by increased generation or by decreased degradation of Abeta. Therefore, activation of mechanisms that lower brain Abeta levels is considered valuable for AD therapy. Neuronal upregulation of neprilysin (NEP) in young transgenic mice expressing the AD-causing amyloid precursor protein mutations (SwAPP) led to reduction of brain Abeta levels and delayed Abeta plaque deposition. In contrast, a comparable increase of brain NEP levels in aged SwAPP mice with pre-existing plaque pathology did not result in a significant reduction of plaque pathology. Therefore, we suggest that the potential of NEP for AD therapy is age-dependent and most effective early in the course of AD pathophysiology.
authors.affiliation: Division of Psychiatry Research, University of Zurich, August Forel Str. 1, 8008 Zurich, Switzerland. mohajeri@bli.unizh.ch
authors.forename: M Hasan
authors.initials: MH
authors.lastname: Mohajeri
authors.forename: Katrin
authors.initials: K
authors.lastname: Kuehnle
authors.forename: Hong
authors.initials: H
authors.lastname: Li
authors.forename: Raphael
authors.initials: R
authors.lastname: Poirier
authors.forename: Jay
authors.initials: J
authors.lastname: Tracy
authors.forename: Roger M
authors.initials: RM
authors.lastname: Nitsch
mesh_terms: D000367:Age Factors; D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000008:administration & dosage / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000166:cytology / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006801:Humans; D051379:Mice; D015260:Neprilysin / Q000378:metabolism*; D009457:Neuroglia / Q000166:cytology / Q000378:metabolism; D058225:Plaque, Amyloid / Q000378:metabolism* / Q000473:pathology*
chemical_list: D016229:Amyloid beta-Peptides; D015260:Neprilysin