title: Familial Alzheimer's disease genes in Japanese.
abstract: More than 40 missense mutations and a splice-site mutation in the presenilin 1 (PS-1) gene, two missense mutations of presenilin 2 (PS-2), and more than three missense mutations of amyloid precursor protein (APP) cosegregate with early onset familial Alzheimer's disease (FAD). In order to determine the incidence of mutations of these genes in Japanese patients, we screened 25 early onset FAD families, one late-onset FAD case, 33 early onset AD cases and five late-onset AD cases for mutations in the coding regions of the genes using SSCP analysis. Four different missense mutations of the PS-1 gene, including a novel mutation, Glu273Ala, were identified in five early onset FAD families and one missense mutation of PS-1 in one isolated AD patient. While no missense mutations of PS-2 were detected, four silent nucleotide substitutions were observed. Our data indicate that PS-1 mutations account for 20.0% of early onset FAD cases in Japan. Since mutations in PS-2 and APP genes were not found in the remaining cases, which could be explained only partially by apolipoprotein E epsilon4, important FAD genes or risk-factor genes remain to be identified.
authors.affiliation: Department of Demyelinating Disease and Aging, NCNP, Kodaira, Tokyo, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Kamimura
authors.forename: H
authors.initials: H
authors.lastname: Tanahashi
authors.forename: H
authors.initials: H
authors.lastname: Yamanaka
authors.forename: K
authors.initials: K
authors.lastname: Takahashi
authors.forename: T
authors.initials: T
authors.lastname: Asada
authors.forename: T
authors.initials: T
authors.lastname: Tabira
mesh_terms: D000328:Adult; D017668:Age of Onset; D000368:Aged; D000544:Alzheimer Disease / Q000208:ethnology / Q000235:genetics*; D019943:Amino Acid Substitution; D016564:Amyloid beta-Protein Precursor / Q000235:genetics*; D001057:Apolipoproteins E / Q000235:genetics*; D044466:Asian People / Q000235:genetics*; D004252:DNA Mutational Analysis; D006801:Humans; D007564:Japan / Q000453:epidemiology; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D020125:Mutation, Missense; D009419:Nerve Tissue Proteins / Q000235:genetics*; D018807:Polymorphism, Single-Stranded Conformational; D053764:Presenilin-1; D053766:Presenilin-2; D012326:RNA Splicing / Q000235:genetics
chemical_list: D016564:Amyloid beta-Protein Precursor; D001057:Apolipoproteins E; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; C508853:PSEN1 protein, human; C508861:PSEN2 protein, human; D053764:Presenilin-1; D053766:Presenilin-2