title: Presenilin-2 mutation causes early amyloid accumulation and memory impairment in a transgenic mouse model of Alzheimer's disease.
abstract: In order to clarify the pathophysiological role of presenilin-2 (PS2) carrying the Volga German Kindred mutation (N141I) in a conventional mouse model of Alzheimer's disease (AD) expressing amyloid precursor protein (APP) with the Swedish mutation (Tg2576 line), we generated a double transgenic mouse (PS2Tg2576) by crossbreeding the PS2 mutant with Tg2576 mice. Here, we demonstrate that the PS2 mutation induced the early deposition of amyloid β-protein (Aβ) at 2-3 months of age and progressive accumulation at 4-5 months of age in the brains of the mutant mice. The PS2 mutation also accelerated learning and memory impairment associated with Aβ accumulation at 4-5 months of age in Tg2576 mice. These results suggest that the PS2 mutation causes early cerebral amyloid accumulation and memory dysfunction. PS2Tg2576 mice are a suitable mouse model for studying amyloid-lowering therapies.
authors.affiliation: Molecular Gerontology, Tokyo Metropolitan Institute of Gerontology, 35-2 Sakae-Cho, Itabashi-Ku, Tokyo 173-0015, Japan.
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Toda
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Noda
authors.forename: Genzo
authors.initials: G
authors.lastname: Ito
authors.forename: Masahiro
authors.initials: M
authors.lastname: Maeda
authors.forename: Takahiko
authors.initials: T
authors.lastname: Shimizu
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics* / Q000473:pathology; D000682:Amyloid / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D001921:Brain / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D005260:Female; D053208:Kaplan-Meier Estimate; D008136:Longevity; D008297:Male; D018782:Maze Learning; D008569:Memory Disorders / Q000235:genetics*; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation / Q000235:genetics*; D010641:Phenotype; D053766:Presenilin-2 / Q000235:genetics*; D012995:Solubility
chemical_list: D000682:Amyloid; D016229:Amyloid beta-Peptides; D053766:Presenilin-2