Esther Blessing, MD, PhD

My lab studies how diurnal thermoregulation, that is the pattern in which core body and brain temperature change over the daily sleep-wake cycle, affect risks for Alzheimer's Disease (AD) and other neurodegenerative disorders. Our recent first-in-human, first-in-mouse study https://www.jci.org/articles/view/182931 shows that diurnal thermoregulation is a major factor driving parallel rhythms in plasma and CSF tau protein, a core biomarker of AD. Owing to the highly temperature-dependent nature of molecular pathways underlying tau protein production, even the small ~1°C change in brain temperature between sleeping and waking has strong effects on tau protein molecular dynamics underlying tau proteostasis. Results suggest that maintaining a healthy body temperature rhythm (higher during waking and lower during sleep) is important for preventing AD, and that sleep disturbance may be partly increasing AD risk by disturbing body temperature rhythms. Interestingly, early AD changes in the brain affect the neurons that control both body temperature rhythm and sleep; specifically, tau aggregates first form in brainstem and hypothalamic thermoregulatory neurons including the lateral hypothalamic orexin neurons, parabrachial nucleus, and preoptic area, among others. Therefore, body temperature dysregulation may be both a sign and a cause of early AD brain changes.

Our work expands to the role of abnormal thermoregulation in known risk pathways for neurodegenerative disease such as menopause and genetic factors. In our recent work https://academic.oup.com/sleep/article/48/Supplement_1/A21/8135363 we are studying how differences between females and males in how body temperature and slow wave sleep interact lead to sex-specific patterns of sleep. We hope this research will lead to insights in treating menopause related sleep-disturbance and preventing female-specific AD risk pathways. The long-term goals of our research are to use thermal interventions like sleeping cool, exercise, sauna, and pharmacological interventions that alter body temperature to improve sleep and prevent neurodegenerative disease. In our collaboration with the Fortea Lab at the University of Sant Pau, Barcelona, we are studying how body temperature disturbance in Down Syndrome may increase risk for earlier development of Alzheimer's Disease. 

In a second avenue of research, my laboratory runs clinical trials testing the efficacy of cannabidiol for the treatment of stress-related disorders including post-traumatic stress disorder and social anxiety disorder. These studies include precision medicine prediction of treatment response and drug target engagement based upon genomic, transcriptomic, and neural circuit (MR imaging) biomarkers and neuropsychological assessments.