García-Colomo Alejandra, López-Sanz David, Taguas Ignacio, Carrasco-Gómez Martín, Spuch Carlos, Comis-Tuche María, Maestú Fernando
Center for Cognitive and Computational Neuroscience, Complutense University of Madrid, Pozuelo de Alarcón, 28223, Spain.
Department of Experimental Psychology, Cognitive Psychology and Speech & Language Therapy, Complutense University of Madrid, Pozuelo de Alarcón, 28223, Spain.
Alzheimers Res Ther. 2025 Jan 6;17(1):8. doi: 10.1186/s13195-024-01654-x.
Changes in amyloid beta (Aβ) and phosphorylated tau brain levels are known to affect brain network organization but very little is known about how plasma markers can relate to these measures. We aimed to address the relationship between centrality network changes and two plasma pathology markers: phosphorylated tau at threonine 231 (p-tau231), a proxy for early Aβ change, and neurofilament light chain (Nfl), a marker of axonal degeneration.
One hundred and four cognitively unimpaired individuals were divided into a high pathology load (33 individuals; HP) group and a low pathology (71 individuals; LP) one. All participants underwent a magnetoencephalography (MEG) recording, a neuropsychological evaluation and plasma sampling. With the MEG recordings, a compound centrality score for each brain source was calculated that considered both intra- and inter-band links. For each group, the relationship between this centrality score and the two plasma markers was studied by means of correlation analyses. Furthermore, the relationship between the centrality score and the plasma markers among the HP and LP groups was compared. Lastly, we investigated whether hubs were more intensely affected by these changes.
Increasing concentrations of p-tau231, which is a proxy of Aβ pathology, were associated with greater theta centrality score of posterior areas that increased their connectedness in the theta range with the remaining areas, regardless of the latter's frequency range. The opposite relationship was found for left areas that decreased their centrality score in the gamma frequency range. These results only emerged for HP individuals, who showed a significantly different relationship between centrality and p-tau231 compared to LP individuals. Hubs' centrality score in the theta band was significantly more affected by p-tau231 levels compared to less central regions.
Early brain network reorganizations in cognitively unimpaired individuals are associated with elevated plasma p-tau231, a proxy for very early Aβ changes, only among individuals who show signs of a higher pathology load. Posterior centrality score increases in the theta band are congruent with previous literature and theoretical models, while gamma centrality score losses could be associated with inhibitory neuron dysfunction. Hubs were more intensely affected by p-tau231, and changed to a higher degree, thus corroborating hubs' vulnerability.
已知淀粉样蛋白β（Aβ）和磷酸化tau蛋白的脑内水平变化会影响脑网络组织，但对于血浆标志物如何与这些指标相关却知之甚少。我们旨在探讨中心性网络变化与两种血浆病理标志物之间的关系：苏氨酸231位点的磷酸化tau蛋白（p-tau231），它可作为早期Aβ变化的替代指标；以及神经丝轻链（Nfl），一种轴突退变的标志物。
104名认知功能未受损的个体被分为高病理负荷组（33人；HP）和低病理组（71人；LP）。所有参与者均接受了脑磁图（MEG）记录、神经心理学评估和血浆采样。利用MEG记录，计算每个脑源的复合中心性得分，该得分同时考虑了带内和带间连接。对于每组，通过相关性分析研究该中心性得分与两种血浆标志物之间的关系。此外，比较了HP组和LP组中中心性得分与血浆标志物之间的关系。最后，我们研究了枢纽是否受这些变化的影响更为强烈。
p-tau231浓度升高，作为Aβ病理的替代指标，与后部区域更大的θ波中心性得分相关，后部区域在θ波范围内与其余区域的连接性增加，而不论其余区域的频率范围如何。在γ频率范围内，左侧区域的中心性得分降低，呈现相反的关系。这些结果仅在HP个体中出现，与LP个体相比，HP个体在中心性与p-tau231之间表现出显著不同的关系。与中心性较低的区域相比，枢纽在θ波段的中心性得分受p-tau231水平的影响明显更大。
在认知功能未受损的个体中，早期脑网络重组仅在显示出较高病理负荷迹象的个体中，与血浆p-tau231升高相关，p-tau231是非常早期Aβ变化的替代指标。θ波段后部中心性得分增加与先前的文献和理论模型一致，而γ波段中心性得分降低可能与抑制性神经元功能障碍有关。枢纽受p-tau231的影响更为强烈，且变化程度更高，从而证实了枢纽的易损性。
