The effect of the top 20 Alzheimer disease risk genes on gray-matter density and FDG PET brain metabolism.
The effect of the top 20 Alzheimer disease risk genes on gray-matter density and FDG PET brain metabolism.
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DOI：
10.1016/j.dadm.2016.12.003
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发表时间：
2016
影响因子：
5.3
通讯作者：
Apostolova, Liana G
中科院分区：
文献类型：
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作者：
Stage, Eddie;Duran, Tugce;Risacher, Shannon L;Goukasian, Naira;Do, Triet M;West, John D;Wilhalme, Holly;Nho, Kwangsik;Phillips, Meredith;Elashoff, David;Saykin, Andrew J;Apostolova, Liana G
我们分析了前20个阿尔茨海默病（AD）风险基因对灰质密度（GMD）和代谢的影响。在控制年龄、性别和APOE ε4基因型的情况下，我们使用后扣带低代谢和内侧颞叶GMD作为结果，并将所有风险变异作为预测因素，进行逐步线性回归分析。我们使用统计参数映射8在3D中探索结果。SLC24A4/RIN3在合并性和轻度认知障碍（MCI）中是脑GMD的显著预测因子；MCI中的ZCWPW1；ABCA7、EPHA1和INPP5D在AD组中的表达。低代谢的显著预测因子是合并组的EPHA1，正常对照组的SLC24A4/RIN3、NME8和CD2AP。多个变异显示与GMD和脑代谢有关。对于大多数基因来说，这种影响仅限于认知连续体的特定阶段，这表明遗传对AD患者脑代谢和GMD的影响是复杂的，并且依赖于阶段。
We analyzed the effects of the top 20 Alzheimer disease (AD) risk genes on gray-matter density (GMD) and metabolism. We ran stepwise linear regression analysis using posterior cingulate hypometabolism and medial temporal GMD as outcomes and all risk variants as predictors while controlling for age, gender, and APOE ε4 genotype. We explored the results in 3D using Statistical Parametric Mapping 8. Significant predictors of brain GMD were SLC24A4/RIN3 in the pooled and mild cognitive impairment (MCI); ZCWPW1 in the MCI; and ABCA7, EPHA1, and INPP5D in the AD groups. Significant predictors of hypometabolism were EPHA1 in the pooled, and SLC24A4/RIN3, NME8, and CD2AP in the normal control group. Multiple variants showed associations with GMD and brain metabolism. For most genes, the effects were limited to specific stages of the cognitive continuum, indicating that the genetic influences on brain metabolism and GMD in AD are complex and stage dependent.