Systematic review and meta-analysis of Japanese familial Alzheimer's disease and FTDP-17.
Systematic review and meta-analysis of Japanese familial Alzheimer's disease and FTDP-17.
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DOI：
10.1038/jhg.2015.15
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发表时间：
2015-05
影响因子：
3.5
通讯作者：
Ikeuchi T
中科院分区：
文献类型：
--
作者：
Kasuga K;Kikuchi M;Tokutake T;Nakaya A;Tezuka T;Tsukie T;Hara N;Miyashita A;Kuwano R;Ikeuchi T
APP、PSEN 1和PSEN 2的突变作为家族性阿尔茨海默病（FAD）的遗传原因已在不同种族人群中发现。日本人群中已报告了大量具有突变的FAD谱系;然而，目前尚不清楚日本人群中FAD的遗传和临床特征是否与其他人群不同。为了解决这个问题，我们通过文献检索对日本FAD和与17号染色体相关的额颞叶痴呆伴帕金森综合征（FTDP-17）进行了系统回顾和荟萃分析。使用该分析，我们在140例患者中鉴定了39种不同的PSEN 1突变，在35例患者中鉴定了5种APP突变，在84例患者中鉴定了16种MAPT突变。日本患者中没有PSEN 2突变。PSEN 1突变的日本FAD患者的发病年龄明显小于APP突变患者。Kaplan-Meier分析显示，MAPT突变患者的生存期短于PSEN 1或APP突变患者。不同基因突变的患者表现出特征性的临床表现，这表明致病基因的突变可能会改变临床表现。通过收集和编目日本FAD和FTDP-17的遗传和临床信息，我们开发了一个原始数据库，命名为日本家族性阿尔茨海默病数据库，可在http://alzdb.bri.niigata-u.ac.jp/上访问。
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/.