Resting-state network disruption and APOE genotype in Alzheimer's disease: a lagged functional connectivity study.
Resting-state network disruption and APOE genotype in Alzheimer's disease: a lagged functional connectivity study.
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DOI：
10.1371/journal.pone.0046289
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Cacabelos R
中科院分区：
文献类型：
--
作者：
Canuet L;Tellado I;Couceiro V;Fraile C;Fernandez-Novoa L;Ishii R;Takeda M;Cacabelos R
载脂蛋白E β 4（APOE-4）与阿尔茨海默病（AD）的遗传易感性和AD相关的皮质节律异常有关。然而，目前尚不清楚APOE-4是否与疾病发展后或不同阶段大脑内在功能解体的特定模式有关。本研究旨在确定空间模式和APOE基因型对AD患者的静息态振荡和功能连接的影响，使用生理连接指数称为“滞后相位同步”。对125例AD患者和60例老年对照者进行清醒闭眼状态下的静息脑电图（EEG）检查。使用eLORETA测定源电流密度和功能连接性。与对照组相比，AD患者的顶枕区α振荡减少，携带APOE-4等位基因的患者左下顶叶和颞枕区皮质的α活动相对于非携带者减少。AD患者的alpha 2连接模式减少，涉及左侧颞叶和双侧顶叶皮质。几个大脑区域表现出增加滞后相位同步在低频率，特别是在θ波段，跨半球和半球内，其中颞叶连接特别受到损害。大脑皮层连接异常的区域与认知得分相关。在早期AD患者中，我们发现额叶和顶颞区的半球间α连接性出现与APOE-4相关的降低。除了区域性皮质功能障碍外，如异常α振荡所示，AD中还存在影响θ和α带的功能网络中断模式，这些模式与认知障碍水平或APOE基因型相关。这些非线性连接的功能模式可能代表AD的神经生理学或表型标记，并有助于疾病的早期检测。
The apolipoprotein E epsilon 4 (APOE-4) is associated with a genetic vulnerability to Alzheimer's disease (AD) and with AD-related abnormalities in cortical rhythms. However, it is unclear whether APOE-4 is linked to a specific pattern of intrinsic functional disintegration of the brain after the development of the disease or during its different stages. This study aimed at identifying spatial patterns and effects of APOE genotype on resting-state oscillations and functional connectivity in patients with AD, using a physiological connectivity index called “lagged phase synchronization”. Resting EEG was recorded during awake, eyes-closed state in 125 patients with AD and 60 elderly controls. Source current density and functional connectivity were determined using eLORETA. Patients with AD exhibited reduced parieto-occipital alpha oscillations compared with controls, and those carrying the APOE-4 allele had reduced alpha activity in the left inferior parietal and temporo-occipital cortex relative to noncarriers. There was a decreased alpha2 connectivity pattern in AD, involving the left temporal and bilateral parietal cortex. Several brain regions exhibited increased lagged phase synchronization in low frequencies, specifically in the theta band, across and within hemispheres, where temporal lobe connections were particularly compromised. Areas with abnormal theta connectivity correlated with cognitive scores. In patients with early AD, we found an APOE-4-related decrease in interhemispheric alpha connectivity in frontal and parieto-temporal regions. In addition to regional cortical dysfunction, as indicated by abnormal alpha oscillations, there are patterns of functional network disruption affecting theta and alpha bands in AD that associate with the level of cognitive disturbance or with the APOE genotype. These functional patterns of nonlinear connectivity may potentially represent neurophysiological or phenotypic markers of AD, and aid in early detection of the disorder.
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