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.