Gender modulates the APOE ε4 effect in healthy older adults: convergent evidence from functional brain connectivity and spinal fluid tau levels.
Gender modulates the APOE ε4 effect in healthy older adults: convergent evidence from functional brain connectivity and spinal fluid tau levels.
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DOI：
10.1523/jneurosci.0305-12.2012
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发表时间：
2012-06-13
期刊：
影响因子：
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通讯作者：
Alzheimer's Disease Neuroimaging Initiative
中科院分区：
文献类型：
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作者：
Damoiseaux JS;Seeley WW;Zhou J;Shirer WR;Coppola G;Karydas A;Rosen HJ;Miller BL;Kramer JH;Greicius MD;Alzheimer's Disease Neuroimaging Initiative
我们研究了APOE基因型对功能性脑连接的影响是否受健康老年人性别的调节。我们的研究结果证实，与ε3纯合子相比，健康老年APOE ε4携带者的默认模式网络连接显著降低。更重要的是，进一步的测试显示，在楔前叶（一个主要的默认模式枢纽）中，APOE基因型和性别之间存在显著的相互作用。与女性ε3纯合子或男性ε4携带者相比，女性ε4携带者显示出显著降低的默认模式连接性，而男性ε4携带者与男性ε3纯合子的差异最小。使用阿尔茨海默病的独立标志物（即tau的脊髓液水平）对健康老年人的独立样本进行的额外分析为APOE相互作用提供了相应的证据。综上所述，这些结果与先前的研究结果一致，表明阿尔茨海默病女性中ε4等位基因的患病率较高，并且关键地证明了APOE基因型和性别之间的这种相互作用在临床前阶段是可检测的。
We examined whether the effect of APOE genotype on functional brain connectivity is modulated by gender in healthy older human adults. Our results confirm significantly decreased connectivity in the default mode network in healthy older APOE ε4 carriers compared to ε3 homozygotes. More importantly, further testing revealed a significant interaction between APOE genotype and gender in the precuneus, a major default mode hub. Female ε4 carriers showed significantly reduced default mode connectivity compared to either female ε3 homozygotes or male ε4 carriers, whereas male ε4 carriers differed minimally from male ε3 homozygotes. An additional analysis in an independent sample of healthy elderly using an independent marker of Alzheimer’s disease, i.e. spinal fluid levels of tau, provided corresponding evidence for this gender by APOE interaction. Taken together, these results converge with previous work showing a higher prevalence of the ε4 allele among women with Alzheimer’s disease and, critically, demonstrate that this interaction between APOE genotype and gender is detectable in the preclinical period.