Filippini Nicola, MacIntosh Bradley J, Hough Morgan G, Goodwin Guy M, Frisoni Giovanni B, Smith Stephen M, Matthews Paul M, Beckmann Christian F, Mackay Clare E
University Department of Psychiatry, University of Oxford, Oxford OX3 9DU, United Kingdom.
Proc Natl Acad Sci U S A. 2009 Apr 28;106(17):7209-14. doi: 10.1073/pnas.0811879106. Epub 2009 Apr 8.
The APOE epsilon4 allele is a risk factor for late-life pathological changes that is also associated with anatomical and functional brain changes in middle-aged and elderly healthy subjects. We investigated structural and functional effects of the APOE polymorphism in 18 young healthy APOE epsilon4-carriers and 18 matched noncarriers (age range: 20-35 years). Brain activity was studied both at rest and during an encoding memory paradigm using blood oxygen level-dependent fMRI. Resting fMRI revealed increased "default mode network" (involving retrosplenial, medial temporal, and medial-prefrontal cortical areas) coactivation in epsilon4-carriers relative to noncarriers. The encoding task produced greater hippocampal activation in epsilon4-carriers relative to noncarriers. Neither result could be explained by differences in memory performance, brain morphology, or resting cerebral blood flow. The APOE epsilon4 allele modulates brain function decades before any clinical or neurophysiological expression of neurodegenerative processes.
APOEε4等位基因是晚年病理变化的一个风险因素,它也与中老年健康受试者的大脑解剖结构和功能变化有关。我们研究了18名年轻健康的APOEε4携带者和18名匹配的非携带者(年龄范围:20 - 35岁)中APOE基因多态性的结构和功能影响。使用血氧水平依赖性功能磁共振成像(BOLD-fMRI)在静息状态和编码记忆范式期间研究大脑活动。静息态功能磁共振成像显示,与非携带者相比,ε4携带者的“默认模式网络”(涉及压后皮质、内侧颞叶和内侧前额叶皮质区域)共激活增加。编码任务使ε4携带者相对于非携带者的海马激活更强。这两个结果都不能用记忆表现、脑形态或静息脑血流量的差异来解释。APOEε4等位基因在神经退行性过程的任何临床或神经生理学表现出现数十年之前就调节大脑功能。