Dr. Gemma Casadesus is a tenured professor in the Department of Pharmacology & Therapeutics. Her original research focused on the effects of fruits and vegetables on the brain. More specifically, she studied the protective effects of blueberries and their antioxidants on the aging brain and how oxidative stress was a risk factor for Alzheimer’s Disease. Her research now continues to focus on understanding how lifestyle choices or life-long exposures become risk factors for Alzheimer’s Disease. There are several different risk factors that the Casadesus Lab focuses on. Extrinsic factors are those that come from the environment, such as infections, dietary choices, and lifestyle habits. Severe infections or reactions to these infections, like sepsis, can increase the risk of cognitive decline and dementia, especially in elderly patients. Poor diet, obesity, and the resulting development of diabetes are also significant risk factors for Alzheimer’s Disease. Intrinsic factors are those that are internal, such as genetic predispositions, hormonal changes that result from aging or age-related events. For example, menopause in women can increase the risk of Alzheimer’s disease due to the hormonal changes that occur during that time. Aging is another factor as it contributes a diminished ability to protect ourselves from oxidative stress and inflammation which can lead to brain dysfunction. The Casadesus Lab is trying to understand how these changes impact cells and molecules within the brain in such a way that they can lead to brain disfunction and also Alzheimer’s Disease.
Hormones are key molecules that regulate all body functions and organs, including the brain. Therefore, the Casadesus Lab focuses on how metabolic hormones such as insulin, amylin, and leptin and reproductive hormones such as estrogen and gonadotropin hormones, impact brain plasticity and function, particularly in the context of the above-mentioned risk factors. They are researching this using different models, which include manipulating hormone receptors and hormones levels in cells to understand their signaling pathways and Alzheimer’s models to determine if these manipulations prevent the brain dysfunction that can lead to Alzheimer’s.
The lab has been exploring other aspects of disease response, such as sex differences. Females tend to be more resilient to metabolic stress and infection and show better outcomes. However, the female brain, tends to react more vigorously than the male brain during these insults. This hyperactivation can potentially have a negative impact on the brain in the long-term. Dr. Casadesus is interested in understanding what genes cause the male and female brain to respond differently to these insults. With this information, the lab may be able to develop new therapies that target these genes and prevent Alzheimer’s Disease in the future.