Sex differences in in vivo tau neuropathology in a multiethnic sample of late middle-aged adults

Priya Palta, Brady Rippon, Mouna Tahmi, Michelle Pardo, Aubrey Johnson, Zeljko Tomljanovic, Hengda He, Krystal K Laing, Qolamreza R Razlighi, Jeanne A Teresi, Herman Moreno, Adam M Brickman, William C Kreisl, José A Luchsinger, Priya Palta, Brady Rippon, Mouna Tahmi, Michelle Pardo, Aubrey Johnson, Zeljko Tomljanovic, Hengda He, Krystal K Laing, Qolamreza R Razlighi, Jeanne A Teresi, Herman Moreno, Adam M Brickman, William C Kreisl, José A Luchsinger

Abstract

It is unclear whether women have higher brain tau pathology. The objective of this study was to examine whether women have higher tau burden than men, and whether tau differences are independent of amyloid β (Aβ) burden. We conducted a cross-sectional analysis of a multiethnic sample of 252 nondemented late middle-aged (mean age: 64.1 years) adults with tau and amyloid Positron Emission Tomography (PET) data. Tau burden was measured as global standardized uptake value ratio (SUVR) in the middle/inferior temporal gyri and medial temporal cortex with 18F-MK-6240 PET. Aβ was measured as global SUVR with 18F-Florbetaben PET. Women had higher middle/inferior temporal gyri tau SUVR compared to men. However, no sex differences in the medial temporal cortex were observed. Women had higher brain Aβ SUVR compared to men. Continuous Aβ SUVR was positively correlated with medial temporal cortex and middle/inferior temporal gyri tau SUVR. However, there was no evidence of effect modification by Aβ SUVR on sex and tau. Compared with men, women in late middle age show higher tau burden, independent of Aβ.

Keywords: Alzheimer's disease; Epidemiology; Neuroimaging; Sex differences.

Conflict of interest statement

Conflict of Interest/Disclosures

JA Luchsinger receives a stipend from Wolters Kluwer, N.V. as Editor in Chief of the journal Alzheimer’s Disease and Associated Disorders, and has served as a paid consultant to vTv therapeutics, Inc. and Recruitment Partners. AM Brickman is a paid consultant for Regeneron Pharmaceuticals and Cognition Therapeutics, Inc and owns equity in Mars Holding Limited. The other authors have no other conflicts of interests to declare.

Copyright © 2021. Published by Elsevier Inc.

Figures

Figure 1.. Flow chart of participant recruitment.
Figure 1.. Flow chart of participant recruitment.
Figure 2.. Distribution of tau SUVR, overall…
Figure 2.. Distribution of tau SUVR, overall and by sex subgroups.
Black lines in Panels A and C represent non-parametric kernel density estimations for the corresponding tau SUVR measure in the overall sample. Red and blue lines in Panels B and D represent non-parametric kernel density estimations for the corresponding sex within each tau SUVR measure.
Figure 3.. Adjusted Mean Differences in Tau…
Figure 3.. Adjusted Mean Differences in Tau SUVR regions of interest, by sex subgroups.
Boxplots comparing the adjusted means (standard deviation) for tau SUVR from ANCOVA for men and women. Models are adjusted for age.
Figure 4.. Unadjusted bivariate association between (A)…
Figure 4.. Unadjusted bivariate association between (A) medial temporal tau SUVR and Global Aβ SUVR and (B) middle/inferior tau SUVR and Global Aβ SUVR, stratified by sex subgroups.
Red line indicates unadjusted regression association between tau SUVR measures and Global Aβ SUVR among men. Blue line indicates unadjusted regression association between tau SUVR measures and Global Aβ SUVR among women. Dashed line is Aβ positivity according to a k-means clustering algorithm (SUVR=1.367).

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