Female mice destined to develop Alzheimer's-like pathology and related cognitive impairments display a unique pattern of fluctuation in sex hormones during the ovarian cycle, finds new research published in eNeuro. This study suggests the natural reproductive cycle may provide a new window into Alzheimer's Disease (AD) risk among young women.

AD begins to develop decades before the first clinical symptoms emerge. This means the disease may already be progressing during a woman's reproductive years. Researchers asked whether the hormones -- specifically estrogen -- released during the natural ovarian cycle promote disease progression in at-risk individuals.

Despite similarities in cycle length and fertility, the researchers found AD model mice spent a greater portion of time in stages with high estrogen levels than control mice. These stages were associated with impaired learning and memory and abnormal activity in AD-affected brain regions. The researchers also observed a sharp increase in beta-amyloid production during one of the high-estrogen stages. In contrast, progesterone-dominant stages and gonadectomy attenuated these AD-related deficits. Further studies revealed a direct role for estradiol in stimulating neural network excitability and susceptibility to seizures in hAPP mice.

These findings emphasize the importance of incorporating female biology into the study of nervous system disorders.

http://www.eneuro.org/content/early/2018/12/03/ENEURO.0132-17.2018

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