PT - JOURNAL ARTICLE AU - Lauren Broestl AU - Kurtresha Worden AU - Arturo J. Moreno AU - Emily J. Davis AU - Dan Wang AU - Bayardo Garay AU - Tanya Singh AU - Laure Verret AU - Jorge J. Palop AU - Dena B. Dubal TI - Ovarian Cycle Stages Modulate Alzheimer-Related Cognitive and Brain Network Alterations in Female Mice AID - 10.1523/ENEURO.0132-17.2018 DP - 2018 Nov 01 TA - eneuro PG - ENEURO.0132-17.2018 VI - 5 IP - 6 4099 - http://www.eneuro.org/content/5/6/ENEURO.0132-17.2018.short 4100 - http://www.eneuro.org/content/5/6/ENEURO.0132-17.2018.full SO - eNeuro2018 Nov 01; 5 AB - Alzheimer’s disease (AD) begins several decades before the onset of clinical symptoms, at a time when women may still undergo reproductive cycling. Whether ovarian functions alter substrates of AD pathogenesis is unknown. Here we show that ovarian cycle stages significantly modulate AD-related alterations in neural network patterns, cognitive impairments, and pathogenic protein production in the hAPP-J20 mouse model of AD. Female hAPP mice spent more time in estrogen-dominant cycle stages and these ovarian stages worsened AD-related network dysfunction and cognitive impairments. 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 and increasing amyloid beta levels. Understanding dynamic effects of the ovarian cycle on the female nervous system in disease, including AD, is of critical importance and may differ from effects on a healthy brain. The pattern of ovarian cycle effects on disease-related networks, cognition, and pathogenic protein expression may be relevant to young women at risk for AD.