Hashimoto R, Hirata Y, Asada T, Yamashita F, Nemoto K, Mori T, Moriguchi Y, Kunugi H, Arima K, Ohnishi T
Department of Clinical Disorder Research, The Osaka-Hamamatsu Joint Research Center For Child Mental Development, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
Genes Brain Behav. 2009 Feb;8(1):43-52. doi: 10.1111/j.1601-183X.2008.00440.x. Epub 2008 Sep 11.
Genetic factors, such as apolipoprotein E (ApoE) polymorphisms, are thought to play an important role in the etiology of Alzheimer's disease (AD). Recent association studies have suggested that the Val66Met polymorphism in the brain-derived neurotrophic factor (BDNF) gene could play a role in the development of AD. To identify genotypic effects of the BDNF and the ApoE genes on disease progression in preclinical AD, we assessed morphological changes using serial magnetic resonance imaging during the preclinical period of AD in 35 individuals. When all subjects were analyzed as one group, progressive atrophy was noted in the limbic, paralimbic and neocortical areas. Individuals of the BDNF Val/Val genotype showed progressive atrophy in the left medial temporal areas, whereas the BDNF Met allele carriers showed additional changes in the anterior cingulate cortex (ACC), posterior cingulate cortex (PCC) and the precuneus. An interaction between the BDNF genotype and progressive morphological changes was found in the PCC. The noncarriers for the ApoE epsilon4 allele showed progressive atrophy in the bilateral medial temporal areas. In addition to changes in the medial temporal areas, epsilon4 carriers showed progressive atrophy in the PCC, ACC and precuneus. An interaction between the ApoE genotype and progressive morphological change was noted in the right medial temporal area. The present preliminary study indicates that polymorphisms of the ApoE and the BDNF genes could affect disease progression in preclinical AD and implies that the Met-BDNF polymorphism could be an additional risk factor for rapid disease progression in preclinical AD.
遗传因素，如载脂蛋白E（ApoE）多态性，被认为在阿尔茨海默病（AD）的病因中起重要作用。最近的关联研究表明，脑源性神经营养因子（BDNF）基因中的Val66Met多态性可能在AD的发展中起作用。为了确定BDNF和ApoE基因的基因型对临床前AD疾病进展的影响，我们在35名个体的临床前AD期间使用系列磁共振成像评估了形态学变化。当将所有受试者作为一组进行分析时，在边缘叶、边缘旁叶和新皮质区域发现了进行性萎缩。BDNF Val/Val基因型个体在左侧内侧颞叶区域出现进行性萎缩，而BDNF Met等位基因携带者在前扣带回皮质（ACC）、后扣带回皮质（PCC）和楔前叶出现额外变化。在PCC中发现BDNF基因型与进行性形态学变化之间存在相互作用。ApoE ε4等位基因的非携带者在双侧内侧颞叶区域出现进行性萎缩。除了内侧颞叶区域的变化外，ε4携带者在PCC、ACC和楔前叶出现进行性萎缩。在右侧内侧颞叶区域注意到ApoE基因型与进行性形态学变化之间存在相互作用。本初步研究表明，ApoE和BDNF基因的多态性可能影响临床前AD的疾病进展，并暗示Met-BDNF多态性可能是临床前AD疾病快速进展的另一个危险因素。
