The current status of Alzheimer's disease genetics: what do we tell the patients?
The current status of Alzheimer's disease genetics: what do we tell the patients?
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DOI：
10.1016/j.phrs.2003.11.018
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发表时间：
2004-10-01
影响因子：
9.3
通讯作者：
Tanzi, RE
中科院分区：
文献类型：
--
作者：
Bertram, L;Tanzi, RE
阿尔茨海默病（Alzheimer's disease，AD）是一种遗传复杂的异质性疾病。已在三个基因（APP、PSEN 1、PSEN 2）中确定了导致主要早发性家族性AD的完全外显（因果）突变，而对于更常见的迟发性疾病形式，迄今为止仅确定了一个部分外显遗传风险因子（APOE）。一些证据表明，额外的易感基因存在早发性和迟发性AD，然而，没有超过三十个推定的AD基因座提出了日期已在后续分析中一致复制。新的AD基因不仅将为开发新的治疗方法提供有价值的线索，而且还将允许开发新的遗传风险分析策略，这是早期预测/预防这种毁灭性疾病的必要先决条件。本文综述了用于识别复杂疾病中基因的分析工具，并总结了最近的连锁和关联研究结果，表明在几条染色体上存在新的迟发性AD基因。(C)2004爱思唯尔有限公司保留所有权利。
Alzheimer's disease (AD) is a genetically complex and heterogeneous disorder. Fully penetrant (causal) mutations leading to predominantly early-onset familial AD have been identified in three genes (APP, PSEN1, PSEN2), while for the more common late-onset form of the disease, only one partially penetrant genetic risk factor (APOE) has been established to date. Several lines of evidence suggest that additional susceptibility genes exist for both early- and late-onset AD, however, none of the more than three dozen putative AD loci proposed to date have been consistently replicated in follow-up analyses. Novel AD genes will not only provide valuable clues for the development of novel therapeutic approaches, but will also allow the development of new genetic risk profiling strategies that are an essential prerequisite for early prediction/prevention of this devastating disease. This review focuses on the analytic tools used to identify genes in complex diseases, and then provides a summary of recent linkage and association findings indicating the existence of novel late-onset AD genes on several chromosomes. (C) 2004 Elsevier Ltd. All rights reserved.