Abstract
Introduction: The diagnosis of Alzheimer's disease (AD) requires the presence of amyloid and tau pathology, but it remains unclear how they affect the structural network in the pre-clinical stage. We aimed to assess differences in topological properties in cognitively normal (CN) individuals with varying levels of amyloid and tau pathology, as well as their association with AD pathology burden. Methods: A total of 68 CN individuals were included and stratified by normal/abnormal (-/+) amyloid (A) and tau (T) status based on positron emission tomography results, yielding three groups: A-T- (n = 19), A+T- (n = 28), and A+T+ (n = 21). Topological properties were measured from structural connectivity. Group differences and correlations with A and T were evaluated. Results: Compared with the A-T- group, the A+T+ group exhibited changes in the structural network topology. At the global level, higher assortativity was shown in the A+T+ group and was correlated with greater tau burden (r = 0.29, p = 0.02), while no difference in global efficiency was found across the three groups. At the local level, the A+T+ group showed disrupted topological properties in the left hippocampus compared with the A-T- group, characterized by lower local efficiency (p < 0.01) and a lower clustering coefficient (p = 0.014). Conclusions: The increased linkage in the higher level architecture of the white matter network reflected by assortativity may indicate increased brain resilience in the early pathological state. Our results encourage further investigation of the topological properties of the structural network in pre-clinical AD.