The Impact of Sex in Tau‐related AD pathology

TL;DR

This study finds that while men and women have similar tau PET levels, sex influences how other Alzheimer's biomarkers relate to tau in the brain.

Contribution

The study reveals sex-specific differences in the relationship between tau PET, amyloid PET, and plasma p-tau217 biomarkers.

Findings

No sex differences in Tau-PET SUVR levels with Flortaucipir or MK6240 tracers.

Women showed stronger associations between MK6240 Tau PET and Aβ-PET in specific brain regions.

Women had weaker relationships between plasma p-tau217 and Tau PET in early brain regions.

Abstract

Studies suggest that sex influences the deposition of tau in the human brain and impacts on the relationship of tau with AD‐related outcomes. The aim of this study is to evaluate the extent to which sex influences PET‐Tau related outcomes and whether this effect is related to specific tau PET tracers.

We assessed 456 participants from the HEAD study (mean age = 66.07 ± 13.05). All individuals had available Tau‐PET with Flortaucipir and MK6240, Aβ‐PET and a subset had plasma p‐Tau 217 (n = 352). We conducted a linear regression analysis between sex and PET Tau to evaluate the direct influence of sex on PET Tau SUVR. Next, we assessed whether sex affected the relationship between Tau PET (in BRAAK I‐II, III‐IV, V‐VI regions) and Aβ‐PET or plasma p‐Tau 217 by adding an interaction term in the associations. All analyses were corrected by age, clinical classification, and amyloid burden.

No significant differences were observed between male and female SUVR levels in either Flortaucipir and MK6240 tracers (Figure 1). However, when assessing the relationship between Aβ‐PET and Tau, a statistically significant interaction with sex was seen between MK6240 in BRAAK III‐IV (β = 0.160, p = 0.020 ; Figure 2) and BRAAK V‐VI regions (β = 0.196, p = 0.008; Figure 2), with women having a stronger association. Furthermore, we found an interaction between sex and p‐tau217 on Tau PET SUVR in BRAAK regions I‐II using MK6240 or Flortaucipir (β = ‐0.184, p =  0.014; β = ‐0.266, p =  0.002; Figure 3) indicating that women present a weaker relationship between p‐tau217 and Tau PET.

Our results did not show any differences between men and women in Tau‐PET SUVR uptake across tau tracers. However, we found that sex affected how Aβ‐PET and plasma p‐tau217 were associated with Tau‐PET uptake. Further studies are needed to elucidate the underpinnings of the link between sex and the association between these biomarkers.

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