title: Proteolytical processing of mutated human amyloid precursor protein in transgenic mice.
abstract: The evidence that betaA4 is central to the pathology of Alzheimer's disease (AD) came from the identification of several missense mutations in the amyloid precursor protein (APP) gene co-segregating with familial AD (FAD). In an attempt to study the proteolytical processing of mutated human APP in vivo, we have created transgenic mice expressing the human APP695 isoform with four FAD-linked mutations. Expression of the transgene was controlled by the promoter of the HMG-CR gene. Human APP is expressed in the brain of transgenic mice as shown by Western blot and immunohistology. The proteolytic processing of human APP in the transgenic mice leads to the generation of C-terminal APP fragments as well as to the release of betaA4. Despite substantial amounts of betaA4 detected in the brain of the transgenic mice, neither signs of Alzheimer's disease-related pathology nor related behavioural deficits could be demonstrated.
authors.affiliation: Rhône-Poulenc Rorer, Centre de Recherche de Vitry-Alfortville, Vitry-sur-Seine, France.
authors.forename: C
authors.initials: C
authors.lastname: Czech
authors.forename: P
authors.initials: P
authors.lastname: Delaère
authors.forename: A F
authors.initials: AF
authors.lastname: Macq
authors.forename: M
authors.initials: M
authors.lastname: Reibaud
authors.forename: S
authors.initials: S
authors.lastname: Dreisler
authors.forename: N
authors.initials: N
authors.lastname: Touchet
authors.forename: B
authors.initials: B
authors.lastname: Schombert
authors.forename: M
authors.initials: M
authors.lastname: Mazadier
authors.forename: L
authors.initials: L
authors.lastname: Mercken
authors.forename: M
authors.initials: M
authors.lastname: Theisen
authors.forename: L
authors.initials: L
authors.lastname: Pradier
authors.forename: J N
authors.initials: JN
authors.lastname: Octave
authors.forename: K
authors.initials: K
authors.lastname: Beyreuther
authors.forename: G
authors.initials: G
authors.lastname: Tremp
mesh_terms: D016564:Amyloid beta-Protein Precursor / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000378:metabolism*; D007150:Immunohistochemistry; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics*; D011506:Proteins / Q000378:metabolism*
chemical_list: D016564:Amyloid beta-Protein Precursor; D011506:Proteins