Explaining variability in early stages of [18F]-flortaucipir tau-PET binding: Focus on sex differences

Introduction: Female sex is associated with increased [18F]-flortaucipir signal, which may be affected by amyloid pathology, age, and off-target binding in skull and meninges.

Methods: In this cross-sectional study comprising 52 females and 52 matched males, we examined sex-related differences in regional tau-positron emission tomography (PET) with and without considering off-target binding. We assessed the respective contributions of sex, age, amyloid-PET burden, and off-target binding to tau-PET signal. We explored associations between age at menopause and hormone replacement therapy (HRT) use with regional tau-PET signals.

Results: Female sex was associated with increased regional tau both independently and interactively with amyloid, but amyloid-independent associations were largely reduced when controlling for off-target binding. Age but not age*sex interactions explained a small but significant amount of tau-PET signal in temporoparietal regions. Considering the sample size and limited range of amyloid-PET burden, no clear associations between regional tau-PET signals and age at menopause or HRT use could be found.

Discussion: Female sex is associated with increased [18F]-flortaucipir signal mainly through its interaction with amyloid.