Dell'Acqua Flavio, Khan Wasim, Gottlieb Natalie, Giampietro Vincent, Ginestet Cedric, Bouls David, Newhouse Steven, Dobson Richard, Banaschewski Tobias, Barker Gareth J, Bokde Arun L W, Büchel Christian, Conrod Patricia, Flor Herta, Frouin Vincent, Garavan Hugh, Gowland Penny, Heinz Anreas, Lemaítre Hervé, Nees Frauke, Paus Tomas, Pausova Zdenka, Rietschel Marcella, Smolka Michael N, Ströhle Andreas, Gallinat Jean, Westman Eric, Schumann Gunther, Lovestone Simon, Simmons Andrew
King's College London, Institute of Psychiatry, London, UK.
NIHR Biomedical Research Centre for Mental Health, King's College London, London, UK.
J Alzheimers Dis. 2015;47(4):977-84. doi: 10.3233/JAD-140519.
The apolipoprotein E (APOE) ɛ4 allele is the best established genetic risk factor for Alzheimer's disease (AD) and has been previously associated with alterations in structural gray matter and changes in functional brain activity in healthy middle-aged individuals and older non-demented subjects. In order to determine the neural mechanism by which APOE polymorphisms affect white matter (WM) structure, we investigated the diffusion characteristics of WM tracts in carriers and non-carriers of the APOE ɛ4 and ɛ2 alleles using an unbiased whole brain analysis technique (Tract Based Spatial Statistics) in a healthy young adolescent (14 years) cohort. A large sample of healthy young adolescents (n = 575) were selected from the European neuroimaging-genetics IMAGEN study with available APOE status and accompanying diffusion imaging data. MR Diffusion data was acquired on 3T systems using 32 diffusion-weighted (DW) directions and 4 non-DW volumes (b-value = 1,300 s/mm² and isotropic resolution of 2.4×2.4×2.4 mm). No significant differences in WM structure were found in diffusion indices between carriers and non-carriers of the APOE ɛ4 and ɛ2 alleles, and dose-dependent effects of these variants were not established, suggesting that differences in WM structure are not modulated by the APOE polymorphism. In conclusion, our results suggest that microstructural properties of WM structure are not associated with the APOE ɛ4 and ɛ2 alleles in young adolescence, suggesting that the neural effects of these variants are not evident in 14-year-olds and may only develop later in life.
载脂蛋白E（APOE）ɛ4等位基因是阿尔茨海默病（AD）最确定的遗传风险因素，此前已与健康中年个体和老年非痴呆受试者的脑灰质结构改变及脑功能活动变化相关。为了确定APOE基因多态性影响白质（WM）结构的神经机制，我们使用无偏全脑分析技术（基于体素的空间统计学），在一个健康青少年（14岁）队列中研究了APOEɛ4和ɛ2等位基因携带者和非携带者的WM束扩散特征。从欧洲神经影像学-遗传学IMAGEN研究中选取了大量有APOE状态及相应扩散成像数据的健康青少年（n = 575）。在3T系统上采集磁共振扩散数据，使用32个扩散加权（DW）方向和4个非DW容积（b值 = 1300 s/mm²，各向同性分辨率为2.4×2.4×2.4 mm）。在APOEɛ4和ɛ2等位基因携带者和非携带者之间，未发现扩散指数在WM结构上有显著差异，且未确定这些变异的剂量依赖性效应，这表明WM结构差异不受APOE基因多态性调节。总之，我们的结果表明，在青少年时期，WM结构的微观结构特性与APOEɛ4和ɛ2等位基因无关，这表明这些变异的神经效应在14岁时并不明显，可能在生命后期才会显现。
