APOE is associated with age-of-onset, but not cognitive functioning, in late-life depression
APOE is associated with age-of-onset, but not cognitive functioning, in late-life depression
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DOI：
10.1002/gps.1006
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发表时间：
2003-12-01
影响因子：
4
通讯作者：
DeKosky, ST
中科院分区：
文献类型：
--
作者：
Butters, MA;Sweet, RA;DeKosky, ST
目的老年抑郁症（LLD）与进行性痴呆之间的关系是公认的，但了解甚少。与LLD同时发生的认知障碍和首次终生抑郁发作的晚发年龄似乎与随后的进行性痴呆相关。重度抑郁症的历史，特别是当第一次发作发生在晚年，已被确定为阿尔茨海默病（AD）的危险因素。散发性AD的主要遗传危险因素是携带一个或多个载脂蛋白E4（APOE 4）等位基因。我们假设LLD和痴呆风险之间的关联是由APOE 4介导的，特别是APOE 4等位基因频率与认知障碍和较晚的抑郁发作年龄相关。方法比较160例LLD组、568例AD组和老年对照组APOE 2、APOE 3和APOE 4等位基因的分布（欧共体; n = 156）结果认知功能受损LLD亚组的等位基因分布与认知功能正常亚组或EC亚组无差异但与AD组不同。然而，APOE 4携带者抑郁症的平均发病年龄（51.4 +/- 20.7）显著低于非携带者（58.8 +/- 16.8）。在LLD整体的等位基因分布是显着不同的AD，但不是EC group.Conclusions的发现，无论是LLD，伴随认知功能障碍，也不晚发病年龄与APOE 4等位基因频率增加表明，LLD作为一个危险因素，发展中国家的AD以及非AD痴呆通过独立的机制APOE 4。在APOE 4携带者中LLD的发病年龄显著降低的意外发现与APOE 4和AD发病年龄之间的相关性相似。表明APOE 4与抑郁症发病年龄较早相关。版权所有（C）2003约翰威利父子有限公司。
Objective There is a recognized but poorly understood relationship between late-life depression (LLD) and progressive dementia. Both cognitive impairment co-occurring with LLD and a late age-of-onset of first lifetime depressive episode appear to be associated with subsequent progressive dementia. A history of major depression, especially when the first onset occurs in late-life, has been identified as a risk factor for Alzheimer's disease (AD). The major genetic risk factor for sporadic AD is carrying one or more apolipoprotein E4 (APOE4) alleles. We hypothesized that the association between LLD and dementia risk would be mediated by APOE4, specifically that APOE4 allele frequency would be associated with cognitive impairment and later age-of-depression-onset. We also predicted that APOE4 allele frequency would be increased among subjects with LLD.Methods We compared the distribution of APOE2, APOE3, and APOE4 alleles in groups of LLD (n = 160), AD (n = 568) and elderly control (EC; n = 156) subjects.Results The allele distribution of the cognitively impaired LLD subgroup was not different from either the cognitively normal subgroup or the EC group but was different from the AD group. However, mean age-of-onset of depression in APOE4 carriers (51.4 +/- 20.7) was significantly lower than non-carriers (58.8 +/- 16.8). The allele distribution in LLD overall was significantly different from the AD but not the EC group.Conclusions The finding that neither LLD, accompanying cognitive impairment, nor late age-of-onset was associated with an increased APOE4 allele frequency suggests that LLD acts as a risk factor for developing AD as well as non-AD dementia through mechanisms independent of APOE4. The unexpected finding that age-of-onset of LLD was significantly reduced in APOE4 carriers is similar to the association between APOE4 and age-of-onset in AD. Replication of the association of APOE4 with earlier age-of-depression-onset is indicated. Copyright (C) 2003 John Wiley Sons, Ltd.