Tau deposition is associated with grey matter network breakdown across different stages of the Alzheimer’s disease continuum

Background Changes in grey matter covariance networks have been reported in preclinical and clinical stages of Alzheimer’s disease (AD), and have been associated with amyloid‐β (Aβ) deposition and cognitive decline. However, the role of tau pathology on grey matter networks remains unclear. Based on previously reported associations between tau pathology, synaptic density and brain structural measures, tau‐related connectivity changes across different stages of AD might be expected. Method In this study, we examined the relationship between tau aggregation (using tau positron emission tomography [tau‐PET]) and grey matter networks (using T1‐weighted images) in 533 individuals (178 Aβ‐negative cognitively unimpaired (CU) subjects, 105 Aβ‐positive CU subjects (preclinical AD), 122 Aβ‐positive patients with mild cognitive impairment (prodromal AD), and 128 patients with AD dementia) from the Swedish BioFINDER‐2 study (Table 1). Single‐subject grey matter networks were extracted and graph theory properties including degree, connectivity density, clustering coefficient, path length, and small world topology were calculated. Associations between tau‐PET values and global and regional network measures were examined using linear regression models adjusted for age, sex, total intracranial volume, and connectivity density. Result Across the whole sample, we found that higher tau load in the temporal meta‐ROI was associated with significant changes in degree, connectivity density, clustering, path length, and small world values of the brain network (all p < 0.001; Fig. 1, 2), indicative of a less optimal network organization. Already in early disease stages, higher tau PET signal was associated with lower clustering and path length (Table 2). In more advanced disease stages elevated tau pathology was progressively associated with more advanced brain network abnormalities. Conclusion These findings suggest that tau pathology is associated with a reduced communication between neighbouring brain areas and an altered ability to integrate information from distributed brain regions indicative of a more random network topology across different AD stages.