title: Systematic review and meta-analysis of Japanese familial Alzheimer's disease and FTDP-17.
abstract: Mutations in APP, PSEN1 and PSEN2 as the genetic causes of familial Alzheimer's disease (FAD) have been found in various ethnic populations. A substantial number of FAD pedigrees with mutations have been reported in the Japanese population; however, it remains unclear whether the genetic and clinical features of FAD in the Japanese population differ from those in other populations. To address this issue, we conducted a systematic review and meta-analysis of Japanese FAD and frontotemporal dementia with parkinsonism linked to chromosome 17 (FTDP-17) by literature search. Using this analysis, we identified 39 different PSEN1 mutations in 140 patients, 5 APP mutations in 35 patients and 16 MAPT mutations in 84 patients. There was no PSEN2 mutation among Japanese patients. The age at onset in Japanese FAD patients with PSEN1 mutations was significantly younger than that in patients with APP mutations. Kaplan-Meier analysis revealed that patients with MAPT mutations showed a shorter survival than patients with PSEN1 or APP mutations. Patients with mutations in different genes exhibit characteristic clinical presentations, suggesting that mutations in causative genes may modify the clinical presentations. By collecting and cataloging genetic and clinical information on Japanese FAD and FTDP-17, we developed an original database designated as Japanese Familial Alzheimer's Disease Database, which is accessible at http://alzdb.bri.niigata-u.ac.jp/.
authors.affiliation: 1] Department of Molecular Genetics, Brain Research Institute, Niigata University, Niigata, Japan [2] Center for Transdisciplinary Research, Niigata University, Niigata, Japan.
authors.forename: Kensaku
authors.initials: K
authors.lastname: Kasuga
authors.affiliation: 1] Department of Molecular Genetics, Brain Research Institute, Niigata University, Niigata, Japan [2] Research Association for Biotechnology, Tokyo, Japan.
authors.forename: Masataka
authors.initials: M
authors.lastname: Kikuchi
authors.affiliation: Department of Neurology, Brain Research Institute, Niigata University, Niigata, Japan.
authors.forename: Takayoshi
authors.initials: T
authors.lastname: Tokutake
authors.affiliation: 1] Department of Molecular Genetics, Brain Research Institute, Niigata University, Niigata, Japan [2] Department of Genome Informatics, Graduate School of Medicine, Osaka University, Osaka, Japan.
authors.forename: Akihiro
authors.initials: A
authors.lastname: Nakaya
authors.affiliation: Department of Neurology, Brain Research Institute, Niigata University, Niigata, Japan.
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Tezuka
authors.affiliation: 1] Department of Molecular Genetics, Brain Research Institute, Niigata University, Niigata, Japan [2] Research Association for Biotechnology, Tokyo, Japan.
authors.forename: Tamao
authors.initials: T
authors.lastname: Tsukie
authors.affiliation: Department of Molecular Genetics, Brain Research Institute, Niigata University, Niigata, Japan.
authors.forename: Norikazu
authors.initials: N
authors.lastname: Hara
authors.affiliation: Department of Molecular Genetics, Brain Research Institute, Niigata University, Niigata, Japan.
authors.forename: Akinori
authors.identifier: 0000000325089649
authors.initials: A
authors.lastname: Miyashita
authors.affiliation: Department of Molecular Genetics, Brain Research Institute, Niigata University, Niigata, Japan.
authors.forename: Ryozo
authors.initials: R
authors.lastname: Kuwano
authors.affiliation: Department of Molecular Genetics, Brain Research Institute, Niigata University, Niigata, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Ikeuchi
mesh_terms: D017668:Age of Onset; D000544:Alzheimer Disease / Q000235:genetics* / Q000473:pathology / Q000523:psychology; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics; D057180:Frontotemporal Dementia / Q000235:genetics* / Q000473:pathology / Q000523:psychology; D020022:Genetic Predisposition to Disease; D006801:Humans; D009154:Mutation