title: Cellular prion protein modulates β-amyloid deposition in aged APP/PS1 transgenic mice.
abstract: Alzheimer's disease and prion diseases are neuropathological disorders that are caused by abnormal processing and aggregation of amyloid and prion proteins. Interactions between amyloid precursor protein (APP) and PrP(c) proteins have been described at the neuron level. Accordingly to this putative interaction, we investigated whether β-amyloid accumulation may affect prion infectivity and, conversely, whether different amounts of PrP may affect β-amyloid accumulation. For this purpose, we used the APPswe/PS1dE9 mouse line, a common model of Alzheimer's disease, crossed with mice that either overexpress (Tga20) or that lack prion protein (knock-out) to generate mice that express varying amounts of prion protein and deposit β-amyloid. On these mouse lines, we investigated the influence of each protein on the evolution of both diseases. Our results indicated that although the presence of APP/PS1 and β-amyloid accumulation had no effect on prion infectivity, the accumulation of β-amyloid deposits was dependent on PrP(c), whereby increasing levels of prion protein were accompanied by a significant increase in β-amyloid aggregation associated with aging.
authors.affiliation: Centro de Biología Molecular "Severo Ochoa", Madrid, Spain; Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain.
authors.forename: Lara
authors.initials: L
authors.lastname: Ordóñez-Gutiérrez
authors.forename: Juan María
authors.initials: JM
authors.lastname: Torres
authors.forename: Rosalina
authors.initials: R
authors.lastname: Gavín
authors.forename: Marta
authors.initials: M
authors.lastname: Antón
authors.forename: Ana Isabel
authors.initials: AI
authors.lastname: Arroba-Espinosa
authors.forename: Juan-Carlos
authors.initials: JC
authors.lastname: Espinosa
authors.forename: Cristina
authors.initials: C
authors.lastname: Vergara
authors.forename: José A
authors.initials: JA
authors.lastname: Del Río
authors.forename: Francisco
authors.initials: F
authors.lastname: Wandosell
mesh_terms: D000375:Aging / Q000235:genetics* / Q000378:metabolism*; D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000502:physiology*; D000818:Animals; D004195:Disease Models, Animal; D051379:Mice; D008822:Mice, Transgenic; D018621:PrPC Proteins / Q000502:physiology*; D053764:Presenilin-1 / Q000502:physiology; D011328:Prions / Q000378:metabolism / Q000472:pathogenicity
chemical_list: D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D018621:PrPC Proteins; D053764:Presenilin-1; D011328:Prions
keywords: Aging; Amyloid; Neurodegeneration; Prion; Signaling