title: A novel Polish presenilin-1 mutation (P117L) is associated with familial Alzheimer's disease and leads to death as early as the age of 28 years.
abstract: The majority of early-onset familial Alzheimer's disease (FAD) is associated with mutations in the presenilin-1 (PS1) gene. We describe a novel Polish PS1 mutation of Pro117Leu, associated with the earliest average age of onset and death so far reported in a PS-linked, FAD kindred. Human kidney 293 and mouse neuroblastoma N2a cells were stably transfected with wild-type and PS1 P117L. There was a significant increase in the amyloid beta42/40 ratio in the N2a P117L PS1 transfected cells compared with N2a transfected with wild-type PS1. What role PS has in the pathogenesis of AD remains to be determined, however, the severity of the clinical picture associated with this PS1 mutation stresses the importance of presenilin.
authors.affiliation: Department of Neurology, New York University Medical Center, NY 10016, USA.
authors.forename: T
authors.initials: T
authors.lastname: Wisniewski
authors.forename: W K
authors.initials: WK
authors.lastname: Dowjat
authors.forename: J D
authors.initials: JD
authors.lastname: Buxbaum
authors.forename: O
authors.initials: O
authors.lastname: Khorkova
authors.forename: S
authors.initials: S
authors.lastname: Efthimiopoulos
authors.forename: J
authors.initials: J
authors.lastname: Kulczycki
authors.forename: W
authors.initials: W
authors.lastname: Lojkowska
authors.forename: J
authors.initials: J
authors.lastname: Wegiel
authors.forename: H M
authors.initials: HM
authors.lastname: Wisniewski
authors.forename: B
authors.initials: B
authors.lastname: Frangione
mesh_terms: D000328:Adult; D000544:Alzheimer Disease / Q000235:genetics* / Q000401:mortality; D015153:Blotting, Western; D002478:Cells, Cultured; D004247:DNA / Q000032:analysis; D005260:Female; D006801:Humans; D008017:Life Expectancy; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D009154:Mutation / Q000502:physiology*; D010375:Pedigree; D016133:Polymerase Chain Reaction; D053764:Presenilin-1; D014162:Transfection / Q000235:genetics
chemical_list: D008565:Membrane Proteins; C508853:PSEN1 protein, human; D053764:Presenilin-1; D004247:DNA