title: Age-related CNS disorder and early death in transgenic FVB/N mice overexpressing Alzheimer amyloid precursor proteins.
abstract: Transgenic FVB/N mice overexpressing human (Hu) or mouse (Mo) Alzheimer amyloid precursor protein (APP695) die early and develop a CNS disorder that includes neophobia and impaired spatial alternation, with diminished glucose utilization and astrogliosis mainly in the cerebrum. Age at onset of neophobia and age at death decrease with increasing levels of brain APP. HuAPP transgenes induce death much earlier than MoAPP transgenes expressed at similar levels. No extracellular amyloid was detected, indicating that some deleterious processes related to APP overexpression are dissociated from formation of amyloid. A similar clinical syndrome occurs spontaneously in approximately 20% of nontransgenic mice when they reach mid- to late-adult life, suggesting that APP overexpression may accelerate a naturally occurring age-related CNS disorder in FVB/N mice.
authors.affiliation: Department of Neurology, University of Minnesota, Minneapolis 55455, USA.
authors.forename: K K
authors.initials: KK
authors.lastname: Hsiao
authors.forename: D R
authors.initials: DR
authors.lastname: Borchelt
authors.forename: K
authors.initials: K
authors.lastname: Olson
authors.forename: R
authors.initials: R
authors.lastname: Johannsdottir
authors.forename: C
authors.initials: C
authors.lastname: Kitt
authors.forename: W
authors.initials: W
authors.lastname: Yunis
authors.forename: S
authors.initials: S
authors.lastname: Xu
authors.forename: C
authors.initials: C
authors.lastname: Eckman
authors.forename: S
authors.initials: S
authors.lastname: Younkin
authors.forename: D
authors.initials: D
authors.lastname: Price
mesh_terms: D000375:Aging; D000544:Alzheimer Disease; D016564:Amyloid beta-Protein Precursor / Q000235:genetics*; D000818:Animals; D001253:Astrocytes / Q000473:pathology; D001483:Base Sequence; D001522:Behavior, Animal; D001921:Brain / Q000378:metabolism / Q000473:pathology; D002493:Central Nervous System Diseases / Q000235:genetics* / Q000401:mortality / Q000503:physiopathology; D003360:Cosmids; D005260:Female; D015870:Gene Expression; D005822:Genetic Vectors; D005947:Glucose / Q000378:metabolism; D006801:Humans; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data
chemical_list: D016564:Amyloid beta-Protein Precursor; D005947:Glucose