Sex differences in ß-amyloid accumulation in 3xTg-AD mice: role of neonatal sex steroid hormone exposure.

ABSTRACT

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 ß-amyloid (Aß) pathology in male and female triple transgenic (3xTg-AD) mice. We found that female 3xTg-AD mice exhibit significantly greater Aß 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 Aß pathology. We observed that male 3xTg-AD mice demasculinized during early development exhibit significantly increased Aß accumulation in adulthood. In contrast, female mice defeminized during early development exhibit a more male-like pattern of Aß 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.