Sexual Dimorphism in Physiological, Metabolic, and Hypothalamic Alterations in the Tg-SwDI Mouse Model of Alzheimer's Disease

Sexual Dimorphism in Physiological, Metabolic, and Hypothalamic Alterations in the Tg-SwDI Mouse Model of Alzheimer's Disease

Alvin Sherman Library

Alzheimer's disease (AD) is a neurodegenerative disorder affecting 55 million people worldwide. Cognitive disruptions, linked to pathology in the hippocampus and cortical areas, are frequently observed in individuals with late manifestation of AD; however, non-cognitive dysfunctions, which contribute to poor quality of life and survival, are often overlooked. The hypothalamus plays a role in regulating homeostatic functions such as hunger, thirst, sleep, and blood pressure. The coordinated activity of hypothalamic regions such as the paraventricular nucleus, arcuate nucleus, ventromedial nucleus, dorsomedial nucleus, and lateral hypothalamus are crucial in maintaining metabolic homeostasis and neuroendocrine processes. Dysregulation of these processes has been shown to directly correlate with amyloid-β and tau pathology found in the hypothalamus of AD brains, as well as attenuation of hypothalamic volume and metabolism. Proceeding the late stages of the disease, this disruption often leads to significant late-life weight loss, alterations in feeding behavior, autonomic dysregulation, and disruptions to circadian rhythms many years before cognitive impairment. Previously, we reported sex differences in metabolic and hypothalamic disturbances in a transgenic mouse model of AD (3xTg-AD mice). Here, we investigated physiological and cardiometabolic outcomes in male versus female Tg-SwDI mice (AD model) compared to wild-type controls (C57BL/6J mice) at 7-8 and 13-14 months of age. Further insight into the cardiometabolic differences and mechanisms, as well as the role of biological sex, may pave the way for new opportunities in treatment targets and biomarker development.