title: Abeta 42-induced increase in neprilysin is associated with prevention of amyloid plaque formation in vivo.
abstract: Brain beta-amyloid plaques are principal targets for the development of treatments designed to slow the progression of Alzheimer's disease. Intracranial injections of synthetic beta-amyloid peptide (Abeta(42)) in transgenic mice expressing the Alzheimer's disease-causing Swedish APP double mutations increased neuronal levels of neprilysin, a metalloendopeptidase that degrades Abeta(42) in vivo, on mRNA and protein level. This increase was associated with significant reductions in brain levels of Abeta and with almost complete prevention of amyloid plaque formation throughout the brain. In addition, astrogliosis normally associated with amyloidosis was significantly reduced. Our results suggest that up-regulation of neprilysin in brain may represent an opportunity to reduce or prevent amyloid plaque formation in vivo.
authors.affiliation: Division of Psychiatry Research, University of Zurich, August Forel Strasse 1, 8008 Zurich, Switzerland. mohajeri@bli.unizh.ch
authors.forename: M Hasan
authors.initials: MH
authors.lastname: Mohajeri
authors.forename: M Axel
authors.initials: MA
authors.lastname: Wollmer
authors.forename: Roger M
authors.initials: RM
authors.lastname: Nitsch
mesh_terms: D016229:Amyloid beta-Peptides / Q000378:metabolism / Q000502:physiology*; D000686:Amyloidosis / Q000517:prevention & control*; D000818:Animals; D001483:Base Sequence; D001921:Brain / Q000378:metabolism; D017931:DNA Primers; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D006868:Hydrolysis; D007074:Immunoglobulin G / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D015260:Neprilysin / Q000096:biosynthesis* / Q000378:metabolism; D010446:Peptide Fragments / Q000378:metabolism / Q000502:physiology*
chemical_list: D016229:Amyloid beta-Peptides; D017931:DNA Primers; D007074:Immunoglobulin G; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D015260:Neprilysin