2015.02.21
Systematic review and meta-analysis of Japanese familial Alzheimer's disease and FTDP-17
（J Hum Genet. 2015 May;60(5):281-3. doi: 10.1038/jhg.2015.15. Epub 2015 Feb 19.）
Kensaku Kasuga1,2,6, Masataka Kikuchi1,3,6, Takayoshi Tokutake4, Akihiro Nakaya1,5, Toshiyuki Tezuka4, Tamao Tsukie1,3, Norikazu Hara1, Akinori Miyashita1, Ryozo Kuwano1 and Takeshi Ikeuchi1
1Department of Molecular Genetics, Brain Research Institute, Niigata University;
2Center for Transdisciplinary Research, Niigata University;
3Research Association for Biotechnology;
4Department of Neurology, Brain Research Institute, Niigata University
5Department of Genome Informatics, Graduate School of Medicine, Osaka University
6These authors contributed equally to this work.
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/.
