title: A novel missense mutation in the presenilin-1 gene in a familial Alzheimer's disease pedigree with abundant amyloid angiopathy.
abstract: A number of missense mutations associated with early-onset familial Alzheimer's disease have been reported in the presenilin-1 gene. The mutations were demonstrated to cluster in specific regions of the the protein. We report here a novel missense mutation at the C-terminus of the third transmembrane domain in the presenilin-1 protein in a family of Japanese origin with early-onset Alzheimer's disease. This mutation is located at a site that is different from the sites at which mutations are known to cluster. Although the clinical phenotype is similar to those of pedigrees associated with other presenilin-1 mutations, postmortem examination of this pedigree revealed heavy amyloid deposits in the walls of small meningeal arteries as well as around small vessels within the brain parenchyma. These results indicate that a mutation at the C-terminus of the third transmembrane domain in the presenilin-1, which is a novel site for mutations, may play a key role in Alzheimer's pathogenesis.
authors.affiliation: Hyogo Institute for Aging Brain and Cognitive Disorders, Himeji, Japan. yasuda@hiabcd.go.jp
authors.forename: M
authors.initials: M
authors.lastname: Yasuda
authors.forename: K
authors.initials: K
authors.lastname: Maeda
authors.forename: Y
authors.initials: Y
authors.lastname: Ikejiri
authors.forename: T
authors.initials: T
authors.lastname: Kawamata
authors.forename: S
authors.initials: S
authors.lastname: Kuroda
authors.forename: C
authors.initials: C
authors.lastname: Tanaka
mesh_terms: D000328:Adult; D000544:Alzheimer Disease / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000032:analysis*; D002536:Cerebral Arteries / Q000473:pathology*; D005192:Family Health; D005260:Female; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008969:Molecular Sequence Data; D010375:Pedigree; D010641:Phenotype; D017354:Point Mutation; D053764:Presenilin-1
chemical_list: D016229:Amyloid beta-Peptides; D008565:Membrane Proteins; C508853:PSEN1 protein, human; D053764:Presenilin-1