Early tau deposition findings support sex differences in AD risk
medwireNews: Researchers have found that clinically healthy women with high amyloid burden have elevated tau deposition compared with men.
“In conjunction with this finding, mounting evidence supports the notion that sex differences in the Alzheimer disease pathologic trajectory may well appear downstream of abnormal amyloid burden in the acceleration of tau deposition and brain atrophy”, Reisa Sperling (Massachusetts General Hospital, Charlestown, USA) and co-researchers comment in JAMA Neurology.
Two cross-sectional cohorts were studied (Harvard Aging Brain Study [HABS] and Alzheimer’s Disease Neuroimaging Initiative [ADNI]), giving a total of 296 individuals, aged an average of 74.2 years, who underwent positron emission tomography (PET) between 2016 and 2018.
In the ADNI cohort, median tau deposition in the entorhinal cortex was 5.8% higher in the 55 women compared with the 48 men and there was a slight elevation in the inferior temporal cortex after adjustment for age.
While this association between sex and regional tau was not replicated in the HABS cohort, tau deposition in the entorhinal cortex was elevated among women versus men in both cohorts when only considering those with higher amyloid-beta burden.
Regression coefficient data for the ADNI cohort showed that the interaction between male sex and amyloid-beta burden explained a significant 34% of the difference in tau deposition, while the same interaction in the HABS cohort explained 33%.
By contrast, there was no sex by apolipoprotein ε4 interaction on regional tau deposition.
The researchers estimated that the global burden of amyloid-beta needed to observe a 10% difference in tau signal in the entorhinal cortex between clinically normal men and women was a distribution volume ratio of 1.2 in the HABS cohort and 1.1 in the ADNI cohort.
“It is possible that a sex-modifying effect on the association between [amyloid-beta] and tau reflects a secondary pathway driven by sex-specific lifestyle determinants, such as cardiovascular disease or inflammation”, suggests the team.
“Further, this association may carry some level of specificity, as other extratemporal regions did not exhibit this interactive [amyloid-beta]-by-sex effect on tau signal.”
Sperling and colleagues also note that the findings were stronger in the ADNI cohort than in the HABS cohort, which they say is possibly because the group was more clinically advanced.
“As such, early tau deposition may be accelerated in women compared with men, with our findings lending support to a growing body of literature that exposes a biological underpinning for sex differences in AD risk”, they say.
By Lucy Piper
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