title: Transgenic mice with Alzheimer presenilin 1 mutations show accelerated neurodegeneration without amyloid plaque formation.
abstract: Familial Alzheimer disease mutations of presenilin 1 (PS-1) enhance the generation of A beta1-42, indicating that PS-1 is involved in amyloidogenesis. However, PS-1 transgenic mice have failed to show amyloid plaques in their brains. Because PS-1 mutations facilitate apoptotic neuronal death in vitro, we did careful quantitative studies in PS-1 transgenic mice and found that neurodegeneration was significantly accelerated in mice older than 13 months (aged mice) with familial Alzheimer disease mutant PS-1, without amyloid plaque formation. However, there were significantly more neurons containing intracellularly deposited A beta42 in aged mutant transgenic mice. Our data indicate that the pathogenic role of the PS-1 mutation is upstream of the amyloid cascade.
authors.affiliation: Department of Demyelinating Disease and Aging, National Institute of Neuroscience, NCNP, Kodaira, Tokyo, Japan.
authors.forename: D H
authors.initials: DH
authors.lastname: Chui
authors.forename: H
authors.initials: H
authors.lastname: Tanahashi
authors.forename: K
authors.initials: K
authors.lastname: Ozawa
authors.forename: S
authors.initials: S
authors.lastname: Ikeda
authors.forename: F
authors.initials: F
authors.lastname: Checler
authors.forename: O
authors.initials: O
authors.lastname: Ueda
authors.forename: H
authors.initials: H
authors.lastname: Suzuki
authors.forename: W
authors.initials: W
authors.lastname: Araki
authors.forename: H
authors.initials: H
authors.lastname: Inoue
authors.forename: K
authors.initials: K
authors.lastname: Shirotani
authors.forename: K
authors.initials: K
authors.lastname: Takahashi
authors.forename: F
authors.initials: F
authors.lastname: Gallyas
authors.forename: T
authors.initials: T
authors.lastname: Tabira
mesh_terms: D000367:Age Factors; D000544:Alzheimer Disease / Q000235:genetics* / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000302:isolation & purification; D000818:Animals; D017209:Apoptosis; D002452:Cell Count; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics*; D051379:Mice; D008822:Mice, Transgenic; D020125:Mutation, Missense; D009474:Neurons / Q000473:pathology*; D010446:Peptide Fragments / Q000302:isolation & purification; D058225:Plaque, Amyloid; D053764:Presenilin-1
chemical_list: D016229:Amyloid beta-Peptides; D008565:Membrane Proteins; C508853:PSEN1 protein, human; D010446:Peptide Fragments; D053764:Presenilin-1; C075222:amyloid beta-protein (1-42)