title: Accelerated amyloid deposition, neurofibrillary degeneration and neuronal loss in double mutant APP/tau transgenic mice.
abstract: Even though the idea that amyloid beta peptide accumulation is the primary event in the pathogenesis of Alzheimer's disease has become the leading hypothesis, the causal link between aberrant amyloid precursor protein processing and tau alterations in this type of dementia remains controversial. We further investigated the role of beta-amyloid production/deposition in tau pathology and neuronal cell death in the mouse brain by crossing Tg2576 and VLW lines expressing human mutant amyloid precursor protein and human mutant tau, respectively. The resulting double transgenic mice showed enhanced amyloid deposition accompanied by neurofibrillary degeneration and overt neuronal loss in selectively vulnerable brain limbic areas. These findings challenge the idea that tau pathology in Alzheimer's disease is merely a downstream effect of amyloid production/deposition and suggest that reciprocal interactions between beta-amyloid and tau alterations may take place in vivo.
authors.affiliation: Departmento de Neurología, Universidad de Navarra, Pamplona, Navarra, Spain.
authors.forename: Elena M
authors.initials: EM
authors.lastname: Ribé
authors.forename: Mar
authors.initials: M
authors.lastname: Pérez
authors.forename: Berta
authors.initials: B
authors.lastname: Puig
authors.forename: Ignasi
authors.initials: I
authors.lastname: Gich
authors.forename: Filip
authors.initials: F
authors.lastname: Lim
authors.forename: Mar
authors.initials: M
authors.lastname: Cuadrado
authors.forename: Teresa
authors.initials: T
authors.lastname: Sesma
authors.forename: Silvia
authors.initials: S
authors.lastname: Catena
authors.forename: Belén
authors.initials: B
authors.lastname: Sánchez
authors.forename: María
authors.initials: M
authors.lastname: Nieto
authors.forename: Pilar
authors.initials: P
authors.lastname: Gómez-Ramos
authors.forename: M Asunción
authors.initials: MA
authors.lastname: Morán
authors.forename: Felipe
authors.initials: F
authors.lastname: Cabodevilla
authors.forename: Lluis
authors.initials: L
authors.lastname: Samaranch
authors.forename: Lourdes
authors.initials: L
authors.lastname: Ortiz
authors.forename: Alberto
authors.initials: A
authors.lastname: Pérez
authors.forename: Isidro
authors.initials: I
authors.lastname: Ferrer
authors.forename: Jesús
authors.initials: J
authors.lastname: Avila
authors.forename: Teresa
authors.initials: T
authors.lastname: Gómez-Isla
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D016229:Amyloid beta-Peptides / Q000096:biosynthesis; D016564:Amyloid beta-Protein Precursor / Q000235:genetics*; D000818:Animals; D001921:Brain / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D016923:Cell Death / Q000235:genetics; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009154:Mutation / Q000235:genetics; D009410:Nerve Degeneration / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D016874:Neurofibrillary Tangles / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D058225:Plaque, Amyloid / Q000235:genetics / Q000378:metabolism*; D016875:tau Proteins / Q000235:genetics*
chemical_list: D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D016875:tau Proteins