Therapeutic Interventions for Alzheimer’s disease. Alzheimer’s disease (AD) affects one in every nine adults age 65 and older and is the sixth leading cause of death in the United States. As the average life expectancy increases, the incidence of AD is expected to increase dramatically. Meanwhile, pharmacologic treatments for AD have been ineffective at slowing or halting the disease. Therefore, it is imperative that alternative therapeutic targets be explored.
Over the course of Alzheimer’s disease, multiple biochemical pathways are perturbed, and a multiple-target approach is likely to be more effective than a single target approach. Using a variety of approaches, we identify therapeutic targets that may reduce the cognitive decline associated with AD. We are also examining whether already FDA-approved drugs can ameliorate memory deficits.
Neuronal Hyperexcitabilty. Alzheimer’s disease is a neurodegenerative disorder that targets connected neuronal networks. Effective regulation of activity in these neural networks is essential; over- or under- stimulation can erode synaptic regulation, leading to alterations in learning and memory, and more concerning, neurodegeneration throughout vulnerable networks. A particularly interesting phenomenon observed in the years preceding AD diagnosis, before neuronal death occurs, is a hyperactivity of the memory network. We use technically innovative approaches to examine alterations in the memory network early during the disease process.
Risk factors for AD. We examine how known risk factors, such as aging (the greatest known risk factor for AD), diabetes, and stroke, increase the likelihood of developing AD later in life. The goal is to not only understand why these factors increase the risk for AD but also how drug therapies may act differently in individuals comorbid for two or more diseases. Preclinical mouse models typically use mice exhibiting only one type of pathology (e.g., AD). Current models do not allow us to determine whether having multiple conditions, such as AD and diabetes, decrease the efficacy of therapeutics or increase in the side effects.
