In Vivo Cellular Imaging and Treatment of Hippocampal Dysfunction in Alzheimer Models

Marc A. Busche, MD, PhD University College London


This proposal aims to identify the earliest neurobiological events underlying the development and progression of Alzheimer’s disease (AD). We will explore in particular the effects that tau and amyloid proteins seen in the brains of patients with AD have on the activity of interacting nerve cells in the hippocampus, a brain region which is known to be important for learning and memory. We will test an innovative therapeutic strategy and evaluate its ability to repair abnormal activities of nerve cells. These studies will not only increase our knowledge about the neurobiology of AD but also accelerate our therapeutic efforts to protect nerve cells and rescue learning and memory functions.

Project Details

Using cutting-edge imaging techniques to monitor brain activity in real time will help us understand and ultimately treat AD.

Within the brain, the hippocampus is an area critically involved in learning and memory, and its dysfunction is a key feature of AD and related neurodegenerative disorders. However, the cellular basis of hippocampal dysfunction in AD is not currently known. 

In this project, we will use high-resolution, laser-based microscopy in novel mouse models of AD to directly image the hippocampus, cell by cell, as it starts to develop disease. We will determine how the impairment of individual nerve cells and their connections contributes to abnormal brain activities including epileptic activity that frequently occurs in individuals with AD. Finally, we will test the effects of a new therapeutic strategy that if successful could be immediately used in clinical trials. 

Our research project is unique and innovative because for the first time we will employ an imaging technique that enables us to generate real-time functional views of nerve cells including their processes in the AD brain. Collectively, the experiments are designed to make a significant impact on our understanding, the treatment and prevention of hippocampal cellular and network dysregulation in AD.