Apolipoprotein E ε4 is associated with disease-specific effects on brain atrophy in Alzheimer's disease and frontotemporal dementia
Apolipoprotein E ε4 is associated with disease-specific effects on brain atrophy in Alzheimer's disease and frontotemporal dementia
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DOI：
10.1073/pnas.0812697106
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发表时间：
2009-02-10
影响因子：
11.1
通讯作者：
Gorno-Tempini, Maria Luisa
中科院分区：
文献类型：
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作者：
Agosta, Federica;Vossel, Keith A.;Gorno-Tempini, Maria Luisa
载脂蛋白epsilon 4(ApoE4)与阿尔茨海默病(AD)密切相关，并与其他几种神经疾病有关。本研究探讨了51例疑似AD患者和31例行为变异型额颞叶痴呆(BvFTD)患者中epsilon 4等位基因携带者状态对脑灰质萎缩模式和疾病严重程度的影响，并与56例健康对照组进行了比较。使用统计参数映射进行基于体素的形态测量。AD组epsilon 4等位基因频率明显高于对照组(P<0.001)，而bvFTD组无显著差异。在任何诊断组中，在epsilon 4等位基因携带者和非携带者之间，没有观察到人口统计学或认知特征的差异。然而，在AD和bvFTD中，与非携带者相比，epsilon 4携带者状态与疾病特定区域更严重的脑萎缩有关。AD epsilon 4携带者双侧顶叶皮质和右侧海马区萎缩程度较大，bvFTD epsilon 4携带者两侧内侧、背外侧和眶前叶、前岛、扣带回皮质萎缩程度较大，右侧占优势。这种区域性的epsilon 4效应与apoE可能在不同的神经退行性疾病中独特地影响形态表达的假设是一致的。Epsilon 4携带者的萎缩模式可能表明他们有更大的临床进展风险。
Apolipoprotein epsilon 4 (apoE4) has been strongly linked with Alzheimer's disease ( AD) and contributes to several other neurological disorders. We investigated the influence of epsilon 4 allele carrier status on the pattern of gray matter atrophy and disease severity in 51 patients with probable AD and 31 patients with behavioral variant frontotemporal dementia (bvFTD), compared with 56 healthy controls. Voxel-based morphometry was performed by using statistical parametric mapping. The epsilon 4 allele frequency was higher in the AD group (P < 0.001) than the controls but not in the bvFTD group. No differences in demographic or cognitive profiles were observed between epsilon 4 allele carriers and noncarriers within any of the diagnostic groups. However, epsilon 4 carrier status was associated with more severe brain atrophy in disease-specific regions compared with noncarriers in both AD and bvFTD. AD epsilon 4 carriers showed greater atrophy in the bilateral parietal cortex and right hippocampus, and bvFTD epsilon 4 carriers demonstrated greater atrophy in the bilateral medial, dorsolateral, and orbital frontal cortex, anterior insula, and cingulate cortex with right predominance. This regional epsilon 4 effect is consistent with the hypothesis that apoE may affect the morphologic expression uniquely in different neurodegenerative diseases. The atrophy patterns in epsilon 4 carriers may indicate that they are at greater risk for clinical progression.