| Title: |
Sex, menopause, and hormone therapy moderate the PET tau and Aβ association in cognitively unimpaired adults with Down Syndrome: Findings from the Alzheimer Biomarkers Consortium — Down Syndrome |
| Authors: |
Coughlan, Gillian T; Yuan, Ziwen; Andrews, Elizabeth J.; Boyle, Rory; Seto, Mabel; Schultz, Stephanie A.; Johnson, Keith A; Sperling, Reisa A; Properzi, Michael J; Ances, Beau; Head, Elizabeth; Buckley, Rachel F. |
| Source: |
Alzheimer's & Dementia ; volume 20, issue S2 ; ISSN 1552-5260 1552-5279 |
| Publisher Information: |
Wiley |
| Publication Year: |
2024 |
| Collection: |
Wiley Online Library (Open Access Articles via Crossref) |
| Description: |
Background Virtually all adults with Down Syndrome(DS) show Alzheimer’s disease(AD)‐related pathologic change by the age of 40 years. While sex differences in Aβ‐dependent tauopathy are apparent during early sporadic AD, sex differences in the DS population remain under‐investigated. Moreover, menopause onset occurs earlier in the DS population (45 years), and it remains unknown whether menopause status and hormone therapy(HT) exposure influences Aβ‐dependent tauopathy in women with DS. In a cognitively unimpaired DS population, we investigated cross‐sectional associations between Aβ and regional tau as a function of sex, menopause‐status, and HT‐exposure. Method 115 cognitively unimpaired individuals from the Alzheimer Biomarkers Consortium—Down Syndrome (Mean Age 37.9; 56 women [48%]; 13 APOE ε4 carriers [11%];Table 1) underwent Pittsburgh Compound‐B/Florbetapir(Aβ‐PET) and Flortaucipir(tau‐PET). Global Aβ was transformed to centiloid scale. 10 (20.6%) women self‐reported as being menopausal. 11 (20.4%) women reported HT exposure. Four a priori tau regions previously demonstrating sex differences in sporadic AD were selected (entorhinal cortex, inferior temporal gyrus, fusiform gyrus, lateral occipital cortex). Linear regressions (covarying age) examined the sex*Aβ interaction for each tau‐PET outcome. Similar models were examined in the subset of women, investigating menopause‐status[not menopausal/menopausal]*Aβ and HT*Aβ interactions. Exploratory whole‐brain vertex‐wise tau‐PET analyses were conducted with sex*Aβ and menopause*Aβ (modelled‐separately) and a FDR threshold p =0.05. Result The sex*Aβ interaction showed a trend level association with tau‐PET, suggesting men exhibit elevated posterior‐temporal and lateral‐occipital tau with higher Aβ, relative to women (Figure 1). The menopause status*Aβ analyses indicated that menopausal women with higher Aβ exhibit significantly elevated temporal, lateral occipital and parietal tau (Figure 2). Sensitivity analyses covarying an age*Aβ interaction ... |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| DOI: |
10.1002/alz.086293 |
| Availability: |
https://doi.org/10.1002/alz.086293 |
| Rights: |
http://creativecommons.org/licenses/by/4.0/ |
| Accession Number: |
edsbas.BF03832D |
| Database: |
BASE |