title: A novel presenilin-1 mutation (Leu85Pro) in early-onset Alzheimer disease with spastic paraparesis.
abstract: BACKGROUND
  Early-onset familial Alzheimer disease is caused by mutations in the amyloid precursor protein (APP), presenilin-1 (PSEN1), or presenilin-2 (PSEN2) genes. Phenotypic diversity has been reported to be associated with various mutations in PSEN1. Various mutations of PSEN1 have been reported in cases of early-onset Alzheimer disease with spastic paraparesis.
  
  
  OBJECTIVE
  To describe a novel mutation in the PSEN1 gene associated with early-onset Alzheimer disease with spastic paraparesis.
  
  
  METHODS
  The patient was a 27-year-old man who developed early-onset dementia with spastic paraparesis. We examined sequences of the PSEN1, PSEN2, and APP genes from the patient and his family. To detect a possible mutation effect on the production of amyloid-beta peptide (Abeta), transfected HEK293 cells were examined for Abeta42 and Abeta40 production.
  
  
  RESULTS
  We found a novel mutation (Leu85Pro) in PSEN1. This mutation influenced the production of Abeta, resulting in a 2-fold elevation of Abeta42 production and of the Abeta42/40 ratio.
  
  
  CONCLUSIONS
  To our knowledge, this is the first report of very early-onset Alzheimer disease with spastic paraparesis and with the visual variant form of the disease, which is associated with visuospatial cognitive disorder. The Leu85Pro mutation in PSEN1 was pathogenic.
authors.affiliation: Department of Neurology, Osaka City University Medical School, Osaka, Japan.
authors.forename: Suzuka
authors.initials: S
authors.lastname: Ataka
authors.forename: Takami
authors.initials: T
authors.lastname: Tomiyama
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Takuma
authors.forename: Takenari
authors.initials: T
authors.lastname: Yamashita
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Shimada
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Tsutada
authors.forename: Koichi
authors.initials: K
authors.lastname: Kawabata
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Mori
authors.forename: Takami
authors.initials: T
authors.lastname: Miki
mesh_terms: D000328:Adult; D017668:Age of Onset; D000544:Alzheimer Disease / Q000150:complications / Q000235:genetics* / Q000503:physiopathology*; D016229:Amyloid beta-Peptides / Q000032:analysis / Q000235:genetics; D004252:DNA Mutational Analysis; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D020336:Paraparesis, Spastic / Q000209:etiology*; D017354:Point Mutation; D053764:Presenilin-1; D014786:Vision Disorders / Q000209:etiology
chemical_list: D016229:Amyloid beta-Peptides; D008565:Membrane Proteins; C508853:PSEN1 protein, human; D053764:Presenilin-1