Spruyt Laure, Mlinarič Tjaša, Dusart Nathalie, Reinartz Mariska, Meade Gabriela, Van Hulle Marc M, Van Laere Koen, Dupont Patrick, Vandenberghe Rik
Laboratory for Cognitive Neurology, Department of Neurosciences, KU Leuven, Leuven 3000, Belgium.
Alzheimer Research Centre KU Leuven, Leuven Brain Institute (LBI), KU Leuven, Leuven 3000, Belgium.
Brain Commun. 2025 Apr 15;7(2):fcaf138. doi: 10.1093/braincomms/fcaf138. eCollection 2025.
Tau aggregation in early affected regions in the asymptomatic stage of Alzheimer's disease marks a transitional phase between stable asymptomatic amyloid positivity and the clinically manifest stage. How this early region tau aggregation covertly affects brain function during this asymptomatic stage remains unclear. In this study, 83 participants underwent a 128 electrodes resting-state EEG, a dynamic 100 min tau PET scan (F-MK6240), an amyloid PET scan, a structural T1 MRI scan and neuropsychological assessment. Tau PET data quality control led to a final sample of 66 subjects. Based on the clinical and cognitive status, amyloid and tau PET biomarkers, the group was composed of 37 cognitively unimpaired amyloid negative subjects, 14 cognitively unimpaired amyloid positive subjects and 15 patients with prodromal Alzheimer's disease. We calculated the average undirected weighted Phase Lag Index in the alpha frequency band with eyes closed and used this as weights for the graph and analysed the global clustering coefficient and characteristic path length in sensor space. As a primary objective, we assessed how these global graph measures correlated with tau PET values, in an defined early metaVOI, comprised of the entorhinal and perirhinal cortex, hippocampus, parahippocampus and fusiform cortex. As secondary analyses, we investigated which specific brain regions were mainly implicated, what the contribution was of amyloid, the effect of electrode density and the relation to cognitive performance. In the overall group and within the cognitively unimpaired amyloid positive subgroup, tau aggregation was associated with a decrease in global clustering coefficient and an increase in characteristic path length. These changes reflect the initial disintegration of the small-world brain network during the transitional phase, even before clinical symptoms are apparent. The correlations are most prominent in the perirhinal cortex, indicating that global deterioration of the network is already present early in the Alzheimer's disease pathology. We obtained similar results with only taking 64 electrodes into account. To conclude, we found that in the asymptomatic stage of Alzheimer's disease, tau PET load in medial temporal cortex is associated with global electrophysiological measures of network disintegration. The study demonstrates the potential value of high-density EEG in the era of biologically defined Alzheimer's disease for characterizing brain function in the asymptomatic stage.
在阿尔茨海默病无症状阶段早期受影响区域的tau蛋白聚集标志着稳定的无症状淀粉样蛋白阳性和临床症状阶段之间的过渡阶段。在这个无症状阶段，这种早期区域的tau蛋白聚集如何暗中影响脑功能仍不清楚。在本研究中，83名参与者接受了128电极静息态脑电图、100分钟动态tau蛋白PET扫描（F-MK6240）、淀粉样蛋白PET扫描、结构T1 MRI扫描和神经心理学评估。tau蛋白PET数据质量控制后最终样本为66名受试者。根据临床和认知状态、淀粉样蛋白和tau蛋白PET生物标志物，该组由37名认知未受损的淀粉样蛋白阴性受试者、14名认知未受损的淀粉样蛋白阳性受试者和15名前驱性阿尔茨海默病患者组成。我们计算了闭眼时α频段的平均无向加权相位滞后指数，并将其用作图的权重，分析了传感器空间中的全局聚类系数和特征路径长度。作为主要目标，我们评估了在由内嗅皮层、嗅周皮层、海马、海马旁回和梭状回组成的定义明确的早期元感兴趣区中，这些全局图测量值与tau蛋白PET值之间的相关性。作为次要分析，我们研究了哪些特定脑区主要受累，淀粉样蛋白的作用是什么，电极密度的影响以及与认知表现的关系。在整个组以及认知未受损的淀粉样蛋白阳性亚组中，tau蛋白聚集与全局聚类系数降低和特征路径长度增加相关。这些变化反映了在过渡阶段，甚至在临床症状出现之前，小世界脑网络的初始解体。相关性在嗅周皮层最为显著，表明在阿尔茨海默病病理早期网络已经出现整体恶化。仅考虑64个电极时我们也得到了类似结果。总之，我们发现在阿尔茨海默病无症状阶段，内侧颞叶皮层的tau蛋白PET负荷与网络解体的全局电生理测量值相关。该研究证明了在生物学定义的阿尔茨海默病时代，高密度脑电图在表征无症状阶段脑功能方面的潜在价值。
