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

Abstract

Introduction We examined networks of tau connectivity between brain regions based on correlations of their [18F]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.

Sex Differences in Cognitive Decline Among US Adults

“…Women might have faster cognitive decline than men because of differences in sex hormones, structural brain development, genetics, psychosocial factors, lifestyle factors, functional connectivity, and tau pathology. 45 , 46 , 47 Women might have greater burden of small vessel disease, including white matter hyperintensity volume, and less axonal structural integrity that in turn leads to faster cognitive decline particularly in executive function and processing speed. 48 , 49 Women also appear to have lower gray matter volume, 50 so they might be more vulnerable to both the accelerated gray volume loss that occurs with aging and the differential volume loss in specific brain regions that occurs with neurodegenerative diseases.…”

An App knock-in rat model for Alzheimer’s disease exhibiting Aβ and tau pathologies, neuronal death and cognitive impairments

“… 101 Third, tau pathologies may spread more in women than in men, particularly in MCI patients. 102 Our App NL-G-F rat model may be highly useful in studying sex differences in AD and their underlying mechanisms.…”

Using the Alzheimer's Disease Neuroimaging Initiative to improve early detection, diagnosis, and treatment of Alzheimer's disease

“…At autopsy, this sex advantage was observed at the earlier Braak stages I/II and III/IV, but no sex differences in verbal memory were observed at late stages V/VI. Interestingly, sex‐specific differences in tau propagation across the brain were observed using tau‐PET to construct tau connectivity networks 132 . The most striking difference was that widespread tau PET uptake increased from CU to MCI to a much greater extent in women than men.…”

“…CN, cognitively unimpaired; hemi., hemisphere; MCI, mild cognitive impairment; PET, positron emission tomography; SUVR, standardized uptake value ratio. Reproduced with permission from Shohouki et al132 AD as a metabolic disease, a recent study investigated how these factors affect associations between AT(N) biomarkers (CSF Aβ42, CSF p-tau181, FDG PET) and metabolites 135. From 139 blood metabolites tested, the study identified and replicated 8 homogeneous (the same between sexes), 15 heterogeneous (differed by sex), and 3 sex-specific interactions with AT(N) biomarkers (FigureS18in supporting information).…”