EuroEspes Biomedical Research Center, Institute for CNS Disorders and Genomic Medicine, Corunna, Spain.
PLoS One. 2012;7(9):e46289. doi: 10.1371/journal.pone.0046289. Epub 2012 Sep 25.
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".
METHODOLOGY/PRINCIPAL FINDINGS: 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.
CONCLUSIONS/SIGNIFICANCE: 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.
载脂蛋白 E ɛ4（APOE-4）与阿尔茨海默病（AD）的遗传易感性以及皮质节律的 AD 相关异常有关。但是，尚不清楚 APOE-4 是否与疾病发展后或不同阶段的大脑内在功能解体的特定模式有关。本研究旨在使用称为“滞后相位同步”的生理连通性指数，确定 APOE 基因型对 AD 患者静息状态振荡和功能连接的空间模式和影响。
方法/主要发现：在 125 名 AD 患者和 60 名老年对照组中，在清醒、闭眼状态下记录静息 EEG。使用 eLORETA 确定源电流密度和功能连接。与对照组相比，AD 患者的顶枕部α振荡减少，携带 APOE-4 等位基因的患者与非携带者相比，左顶下和颞枕皮质的α活动减少。AD 中存在α2 连通性模式减少，涉及左颞叶和双侧顶叶皮质。几个脑区在整个和半球内的低频（特别是θ频段）表现出滞后相位同步增加，其中颞叶连接特别受损。异常θ连通性的区域与认知评分相关。在早期 AD 患者中，我们发现额叶和顶颞区域的 APOE-4 相关的半球间α连通性下降。
结论/意义：除了表明存在异常α振荡的区域皮质功能障碍外，AD 中还存在影响θ和α频段的功能网络破坏模式，与认知障碍程度或 APOE 基因型相关。这些非线性连通性的功能模式可能代表 AD 的神经生理或表型标志物，并有助于早期发现该疾病。
