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

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

doi:10.1016/j.neurobiolaging.2021.03.007

Cited by 19 publications

(20 citation statements)

References 30 publications

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“…Unlike previous findings, we did not see any sex by Aβ‐PET associations with inferior temporal tau 8,16 . A recent cohort of late middle‐aged adults found higher levels of middle and inferior temporal tau in women, 39 but also no interaction between sex and Aβ on regional tau, suggesting that sex by Aβ interactions on tau deposition may appear later in life. We found elevated levels of global Aβ‐PET signal in women, supporting previous findings amongst middle aged adults 22 .…”

Section: Discussioncontrasting

confidence: 99%

“…We found sex differences in regional tau deposition in individuals approximately 20 years younger than those included in prior studies reporting sex differences 11,12,16 . Our findings replicate recent work in a diverse sample of later middle‐aged individuals who also reported sex differences in cortical tau deposition independent of Aβ burden 39 . We extend these findings by reporting Aβ‐independent sex differences in regional tau‐PET deposition in areas not typically found to have early AD‐related tau deposition 7,21,29 .…”

Section: Discussionsupporting

confidence: 86%

“…11,12,16 Our findings replicate recent work in a diverse sample of later middle-aged individuals who also reported sex differences in cortical tau deposition independent of Aβ burden. 39 We extend these findings by reporting Aβ-independent sex differences in regional tau-PET deposition in areas not typically found to have early AD-related tau deposition. 7,21,29 We found no sex by APOEε4 or sex by Aβ-PET interactions associated with tau-PET signal in any of our a priori regions, supporting the hypothesis that sex differences in these regions may not necessarily be influenced by AD-related processes.…”

Section: Discussionsupporting

confidence: 69%

“…These findings introduce a wider implication of what it means to be "tau abnormal" for women relative to men. Given the mounting evidence across multiple independent studies of higher tau in women across cortical regions, 6,7,11,12,16,39 even in middle age, 39 this raises the question of how to understand and interpret tau deposition in women relative to men in observational cohorts as well as clinical trials. At a broad level, this has implications for how we understand tauopathies and the extent to which certain tau species propagate in a sex-specific manner.…”

Section: Discussionmentioning

confidence: 99%

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Menopause Status Moderates Sex Differences in Tau Burden: A Framingham PET Study

Buckley

O’Donnell

McGrath

et al. 2022

Annals of Neurology

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Objective: Women have a higher lifetime risk of Alzheimer's disease (AD) than men. Among cognitively normal (CN) older adults, women exhibit elevated tau positron emission tomography (PET) signal compared with men. We explored whether menopause exacerbates sex differences in tau deposition in middle-aged adults. Methods: 328 CN participants from the Framingham Study (mean age = 57 years (AE10 years), 161 women, of whom, 104 were post-menopausal) underwent tau and β-amyloid (Aβ)-PET neuroimaging. We examined global Aβ-PET, and tau-PET signal in 5 regions identified a priori as demonstrating significant sex differences in older adults (in temporal, inferior parietal, middle frontal, and lateral occipital regions). We examined sex and menopause status-related differences in each region-of-interest, using linear regressions, as well as interactions with Aβ and APOEε4 genotype. Results: Women exhibited higher tau-PET signal (p < 0.002), and global Aβ-PET (p = 0.010), than men in inferior parietal, rostral middle frontal, and lateral occipital regions. Compared with age-matched men, post-menopausal women showed significantly higher tau-PET signal in parieto-occipital regions (p < 0.0001). By contrast, no differences in tau-PET signal existed between pre-menopausal women and men. Aβ-PET was not associated with menopausal status or age. Neither Aβ-PET nor APOEε4 status moderated sex or menopause associations with tau-PET. Interpretation: Clear divergence in tauopathy between the sexes are apparent approximately 20 years earlier than previously reported. Menopause status moderated sex differences in Aβ and tau-PET burden, with tau first appearing post-menopause. Sex and menopause differences consistently appeared in middle frontal and parieto-occipital regions but were not moderated by Aβ burden or APOEε4, suggesting that menopause-related tau vulnerability may be independent of AD-related pathways.

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Section: Discussioncontrasting

confidence: 99%

Section: Discussionsupporting

confidence: 86%

Section: Discussionsupporting

confidence: 69%

Section: Discussionmentioning

confidence: 99%

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Menopause Status Moderates Sex Differences in Tau Burden: A Framingham PET Study

Buckley

O’Donnell

McGrath

et al. 2022

Annals of Neurology

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“…4 Mounting evidence suggests that biological mechanisms underpin sex differences in AD risk and progression. [5][6][7][8][9][10] The APOE gene encodes a protein that transports cholesterol in the blood. 11 APOE ε3 is the most common allele 12 and is neutral in relation to risk for AD dementia.…”

Section: Introductionmentioning

confidence: 99%

Sex differences in associations betweenAPOE ε2and longitudinal cognitive decline

Wood

Xiong

Wong

et al. 2022

Preprint

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INTRODUCTION: We examined whether sex modifies the association between APOE ε2 and cognitive decline across two independent samples. METHODS: We used observational data from non-Hispanic White (NHW) and non-Hispanic Black (NHB) cognitively unimpaired adults. Linear mixed models examined interactive associations of APOE genotype (ε2 or ε4 carrier vs. ε3/ε3) and sex on cognitive decline in NHW and NHB participants separately. RESULTS: In both Sample 1 (N=9,766) and Sample 2 (N=915), sex modified the association between APOE ε2 and cognitive decline in NHW participants. Specifically, relative to APOE ε3/ε3, APOE ε2 protected against cognitive decline in men but not women. Among APOE ε2 carriers, men had slower decline than women. Among APOE ε3/ε3 carriers, cognitive trajectories did not differ between sexes. There were no sex-specific associations of APOE ε2 with cognitive decline in NHB participants (N=2,010). DISCUSSION: In NHW adults, APOE ε2 may selectively protect men against cognitive decline.

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Sex differences in associations between APOE ε2 and longitudinal cognitive decline

Wood

Xiong

Wong

et al. 2023

Alzheimer's & Dementia

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INTRODUCTIONWe examined whether sex modifies the association between APOE ε2 and cognitive decline in two independent samples.METHODSWe used observational data from cognitively unimpaired non‐Hispanic White (NHW) and non‐Hispanic Black (NHB) adults. Linear mixed models examined interactive associations of APOE genotype (ε2 or ε4 carrier vs. ε3/ε3) and sex on cognitive decline in NHW and NHB participants separately.RESULTSIn both Sample 1 (N = 9766) and Sample 2 (N = 915), sex modified the association between APOE ε2 and cognitive decline in NHW participants. Specifically, relative to APOE ε3/ε3, APOE ε2 protected against cognitive decline in men but not women. Among APOE ε2 carriers, men had slower decline than women. Among APOE ε3/ε3 carriers, cognitive trajectories did not differ between sexes. There were no sex‐specific associations of APOE ε2 with cognition in NHB participants (N = 2010).DISCUSSIONIn NHW adults, APOE ε2 may protect men but not women against cognitive decline.Highlights We studied sex‐specific apolipoprotein E (APOE) ε2 effects on cognitive decline. In non‐Hispanic White (NHW) adults, APOE ε2 selectively protects men against decline. Among men, APOE ε2 was more protective than APOE ε3/ε3. In women, APOE ε2 was no more protective than APOE ε3/ε3. Among APOE ε2 carriers, men had slower decline than women. There were no sex‐specific APOE ε2 effects in non‐Hispanic Black (NHB) adults.

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

Cited by 19 publications

References 30 publications

Menopause Status Moderates Sex Differences in Tau Burden: A Framingham PET Study

Menopause Status Moderates Sex Differences in Tau Burden: A Framingham PET Study

Sex differences in associations betweenAPOE ε2and longitudinal cognitive decline

Sex differences in associations between APOE ε2 and longitudinal cognitive decline

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