Genetic and Structural Network Contributions to The Regional Vulnerability of Tauopathy

Tau propagates in a highly stereotyped pattern in both normally aged and cognitively impaired individuals, with the medial temporal lobe (MTL) being first affected. Although substantial progress has been made in revealing its spreading pattern with the aid of network analysis, it remains unclear why tau first seeds in this specific region. We hypothesize that regional white‐matter connections exacerbate MTL’s vulnerability to tauopathy. Further, we speculate that tau candidate genes have higher expression levels in MTL. This study tested the two hypotheses in cognitively normal older brains using two independent imaging datasets, i.e., ADNI and Indiana ADRC (IADRC), along with gene expression data derived from the Allen Human Brain Atlas (AHBA).