Abstract

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.