The risk of Alzheimer's disease (AD) is higher in women than in men, a sex difference that likely results from the effects of sex steroid hormones. To investigate this relationship, we first compared progression of β-amyloid (Aβ) pathology in male and female triple transgenic (3xTg-AD) mice. We found that female 3xTg-AD mice exhibit significantly greater Aβ burden and larger behavioral deficits than age-matched males. Next, we evaluated how the organizational effects of sex steroid hormones during postnatal development may affect adult vulnerability to Aβ pathology. We observed that male 3xTg-AD mice demasculinized during early development exhibit significantly increased Aβ accumulation in adulthood. In contrast, female mice defeminized during early development exhibit a more male-like pattern of Aβ pathology in adulthood. Taken together, these results demonstrate significant sex differences in pathology in 3xTg-AD mice and suggest that these differences may be mediated by organizational actions of sex steroid hormones during development.

作者：Jenna C, Carroll；Emily R, Rosario；Sara, Kreimer；Angela, Villamagna；Elisabet, Gentzschein；Frank Z, Stanczyk；Christian J, Pike

来源：Brain research 2010 年 1366卷