title: PS1 Alzheimer's disease family with spastic paraplegia: the search for a gene modifier.
abstract: PS1 mutations are associated with classic Alzheimer's disease (AD); however, some families develop AD and spastic paraplegia (SP) with brain pathology characterized by Abeta cotton wool plaques. The authors report a variant AD family with the E280Q PS1 mutation. The fact that the same PS1 mutation can be found in patients with either variant or classic AD argues in favor of the presence of a genetic modifier. The authors have excluded that this modifier effect originates from coding sequence variations in three SP genes or from a second mutation in the other AD genes.
authors.affiliation: Centre for Research in Neurodegenerative Diseases, University of Toronto, and Department of Medicine (Division of Neurology), Ontario, Canada. ekaterina.rogaeva@utoronto.ca
authors.forename: E
authors.initials: E
authors.lastname: Rogaeva
authors.forename: C
authors.initials: C
authors.lastname: Bergeron
authors.forename: C
authors.initials: C
authors.lastname: Sato
authors.forename: I
authors.initials: I
authors.lastname: Moliaka
authors.forename: T
authors.initials: T
authors.lastname: Kawarai
authors.forename: A
authors.initials: A
authors.lastname: Toulina
authors.forename: Y-Q
authors.initials: YQ
authors.lastname: Song
authors.forename: T
authors.initials: T
authors.lastname: Kolesnikova
authors.forename: A
authors.initials: A
authors.lastname: Orlacchio
authors.forename: G
authors.initials: G
authors.lastname: Bernardi
authors.forename: P H
authors.initials: PH
authors.lastname: St George-Hyslop
mesh_terms: D017398:Alternative Splicing; D000544:Alzheimer Disease / Q000150:complications / Q000235:genetics* / Q000473:pathology; D001921:Brain / Q000473:pathology; D025063:Chromosome Disorders; D004252:DNA Mutational Analysis; D005190:Family; D005260:Female; D020558:GTP Phosphohydrolases / Q000235:genetics; D019204:GTP-Binding Proteins; D005799:Genes, Dominant; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation; D010264:Paraplegia / Q000150:complications / Q000235:genetics* / Q000473:pathology; D010375:Pedigree; D010641:Phenotype; D058225:Plaque, Amyloid / Q000473:pathology; D011110:Polymorphism, Genetic; D053764:Presenilin-1; D013116:Spinal Cord / Q000473:pathology
chemical_list: D008565:Membrane Proteins; C508853:PSEN1 protein, human; D053764:Presenilin-1; C440006:ATL1 protein, human; D020558:GTP Phosphohydrolases; D019204:GTP-Binding Proteins