Sex modifies the APOE-related risk of developing Alzheimer disease.
Sex modifies the APOE-related risk of developing Alzheimer disease.
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DOI：
10.1002/ana.24135
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发表时间：
2014-04
影响因子：
11.2
通讯作者：
Greicius, Michael D.
中科院分区：
文献类型：
--
作者：
Altmann, Andre;Tian, Lu;Henderson, Victor W.;Greicius, Michael D.
APOE 4等位基因是散发性阿尔茨海默病（AD）最强的遗传危险因素。病例对照研究表明，APOE 4与AD的联系在女性中更强。我们研究了APOE 4与性别在转换风险（从健康老龄到轻度认知障碍（MCI）/AD或从MCI到AD）和脑脊液（CSF）生物标志物水平方面的相互作用。使用考克斯比例风险分析计算对照组（N= 5，496）和MCI患者（N= 2，588）中APOE-性别相互作用对转换的风险比（HR）。还在来自AD神经影像学倡议的980名受试者的CSF生物标志物水平中测试了相互作用。在对照组中，男性和女性携带者更有可能转化为MCI/AD，但女性的影响更强（女性HR=1.81;男性HR=1.27;相互作用P=0.0106）。在限制于APOE 3/3和APOE 3/4基因型的预定义子分析中，相互作用仍然显著。在MCI患者中，男性和女性携带者更容易转化为AD（女性HR=2.16;男性HR=1.64）。这种效应在女性中名义上更强，但相互作用不显著（P=0.136）。在仅限于APOE 3/3和APOE 3/4基因型的子分析中，相互作用显著（P= 0.022;女性HR=2.17;男性HR=1.51）。在MCI患者中，总tau和tau/A β比值的生物标志物水平的APOE 4-性别相互作用显著（分别为P=0.0088和P=0.020;女性中AD样程度更高）。APOE 4在女性中赋予更大的AD风险。生物标志物结果表明，女性APOE相关风险增加可能与tau病理学相关。这些发现具有重要的临床意义，并建议新的研究方法AD发病机制。
The APOE4 allele is the strongest genetic risk factor for sporadic Alzheimer’s disease (AD). Case-control studies suggest the APOE4 link to AD is stronger in women. We examined the APOE4-by-sex interaction in conversion risk (from healthy aging to mild cognitive impairment (MCI)/AD or from MCI to AD) and cerebrospinal fluid (CSF) biomarker levels. Cox proportional hazards analysis was used to compute hazards ratios (HR) for an APOE-by-sex interaction on conversion in controls (N=5,496) and MCI patients (N=2,588). The interaction was also tested in CSF biomarker levels of 980 subjects from the AD Neuroimaging Initiative. Among controls, male and female carriers were more likely to convert to MCI/AD, but the effect was stronger in women (HR=1.81 women; HR=1.27 men; interaction P=0.0106). The interaction remained significant in a pre-defined sub-analysis restricted to APOE3/3 and APOE3/4 genotypes. Among MCI patients, male and female carriers were more likely to convert to AD (HR=2.16 women; HR=1.64 men). The effect was nominally stronger in women, but the interaction was not significant (P=0.136). In the sub-analysis restricted to APOE3/3 and APOE 3/4 genotypes, the interaction was significant (P= 0.022; HR=2.17 women; HR=1.51 men). The APOE4-by-sex interaction on biomarker levels was significant for MCI patients in total-tau and the tau-to-Abeta-ratio (P=0.0088 and P=0.020, respectively; more AD-like in women). APOE4 confers greater AD risk in women. Biomarker results suggest that increased APOE-related risk in women may be associated with tau pathology. These findings have important clinical implications and suggest novel research approaches into AD pathogenesis.
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影响因子：
2.4
作者：
Brainerd, C. J.;Reyna, V. F.;Petersen, R. C.;Smith, G. E.;Kenney, A. E.;Gross, C. J.;Taub, E. S.;Plassman, B. L.;Fisher, G. G.
通讯作者：
Fisher, G. G.
影响因子：
4.2
作者：
Beydoun MA;Boueiz A;Abougergi MS;Kitner-Triolo MH;Beydoun HA;Resnick SM;O'Brien R;Zonderman AB
通讯作者：
Zonderman AB
DOI：
10.1073/pnas.95.18.10914
发表时间：
1998-09-01
影响因子：
11.1
作者：
Raber, J;Wong, D;Mucke, L
通讯作者：
Mucke, L
影响因子：
10.6
作者：
Sunderland, T;Mirza, N;Cohen, RM
通讯作者：
Cohen, RM
影响因子：
2.1
作者：
Bretsky, PM;Buckwalter, JG;Henderson, VW
通讯作者：
Henderson, VW