title: Aging-related down-regulation of neprilysin, a putative beta-amyloid-degrading enzyme, in transgenic Tg2576 Alzheimer-like mouse brain is accompanied by an astroglial upregulation in the vicinity of beta-amyloid plaques.
abstract: Pathological accumulation of cortical beta-amyloid is an early and consistent feature of Alzheimer's disease. Brain level of beta-amyloid is determined both by its production and by its catabolism. Neprilysin, a zinc metalloproteinase has been suggested as potential candidate of beta-amyloid-degrading enzyme in vivo. To address the question whether pathological accumulation of beta-amyloid peptides in transgenic Tg2576 mice with Alzheimer-like pathology may affect beta-amyloid catabolism, the expression of neprilysin was studied during postnatal maturation and aging. Neprilysin protein but mRNA levels decreased in mouse cerebral cortex with age (2-22 months), independently of transgene status. Immunocytochemistry revealed few neprilysin-positive dystrophic neurites around beta-amyloid plaques and an upregulation of neprilysin in plaque-surrounding reactive astrocytes which may suggest a role of plaque-mediated astrogliosis in beta-amyloid degradation.
authors.affiliation: Paul Flechsig Institute for Brain Research, Department of Neurochemistry, University of Leipzig, Jahnallee 59, D-04109 Leipzig, Germany.
authors.forename: Jenny
authors.initials: J
authors.lastname: Apelt
authors.forename: Katrin
authors.initials: K
authors.lastname: Ach
authors.forename: Reinhard
authors.initials: R
authors.lastname: Schliebs
mesh_terms: D000375:Aging / Q000235:genetics / Q000502:physiology*; D000544:Alzheimer Disease / Q000201:enzymology* / Q000235:genetics; D016229:Amyloid beta-Peptides / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001253:Astrocytes / Q000201:enzymology*; D001921:Brain / Q000201:enzymology; D015536:Down-Regulation / Q000502:physiology; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D015260:Neprilysin / Q000235:genetics / Q000378:metabolism*; D058225:Plaque, Amyloid / Q000201:enzymology* / Q000235:genetics; D015854:Up-Regulation / Q000502:physiology
chemical_list: D016229:Amyloid beta-Peptides; D015260:Neprilysin