In vivo network models identify sex differences in the spread of tau pathology across the brain

INTRODUCTION: We examined networks of tau connectivity between brain regions based on correlations of their [(18)F]flortaucipir positron emission tomography (PET) uptake to evaluate sex‐specific differences in brain‐wide tau propagation. METHODS: PET data of clinically normal and mild cognitive impairment (MCI) subjects from the Alzheimer's Disease Neuroimaging Initiative (ADNI) were used to examine differences in network architectures across the groups. RESULTS: The tau‐based network architecture resembled progression of tauopathy from Braak stage I to VI regions. Compared to men, women had higher network density and an increased number of direct regional connections in co‐occurrence with increased brain‐wide tau burden, particularly at MCI. Several regions, including superior parietal lobe and parahippocampus served as connecting bridges between communities at different Braak stages. DISCUSSION: Network characteristics in women may favor an accelerated brain‐wide tau spread leading to a higher tau burden in women than men with MCI with implications for the greater female preponderance in Alzheimer's disease diagnosis.