My research focuses on the mechanisms and reversibility of neuronal degeneration in Alzheimer’s disease and ageing. We hypothesize that the degeneration of synapses, the connections between neuronal cells in the brain, causes memory impairments and that targeting the proteins that cause synaptic degeneration will allow recovery of cognitive function. Previous work from our group has shown that both of the proteins involved in the neuropathological lesions in Alzheimer’s (amyloid beta and tau) contribute to synapse loss in Alzheimer’s disease, and further that reducing the levels of soluble amyloid beta or tau prevents synaptic degeneration and improves memory in disease models. These experiments indicate that the plasticity of synapses will allow recovery after treatments, giving hope for some functional recovery in patients if we can develop therapies that remove the toxic protein species from the brain.
For our experiments, we apply high-resolution imaging techniques, including multiphoton imaging and array tomography, to examine the structure and function of synapses in healthy and diseased brain. Multiphoton microscopy allows imaging of synapses over time to determine the time-course of disease processes and allows for imaging the brain before and after treatments to test candidate therapeutics. Array tomography is a post-mortem imaging technique involving high-throughput imaging of thousands of synapses to determine whether disease-related proteins are associated with synapse shrinkage and loss. We have accumulated the world’s first brain bank of human tissue prepared for the array tomography technique, which we are using to investigate the relationship between synaptic changes and dementia.
Memory is made possible by the ability of synapses, the connections between neurons in the brain, to change in response to environmental inputs. In dementia, memory declines because synapses and neurons become dysfunctional and die. In fact, loss of synapses is a strong predictor of dementia in Alzheimer patients. The goal of our research is to understand why synapses and neurons degenerate in order to develop effective strategies to treat the dementia and other brain diseases.