Dysregulation of hypothalamic pituitary gonadal (HPG) axis signaling with menopause is considered as a risk factor for Alzheimer’s disease (AD). Menopause leads to decreased sex steroid signaling and increased luteinizing hormone signaling which may have profound effects on many cellular processes that predispose to neurodegeneration and impairment in cognitive function. The effects of amyloid production on resting state BOLD fMRI using functional connectivity analysis in a mouse model of AD have been previously published. However how HPG axis dysregulation affect resting state functional connectivity in a mouse model of AD has not been studied. Here we show that ovariectomized AD mice, a commonly used animal model to study menopause related hormonal changes in the HPG axis, exhibit alterations in resting state connectivity in the mouse default mode network connectivity. These findings establish a causal link between AD and HPG axis dysregulation.
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