Aging changes the adult brain both structurally and functionally. Something about these changes increases the risk of Alzheimer’s disease, a neurodegenerative disease that affects millions of Americans and is the leading cause of dementia among adults. Clinical symptoms of Alzheimer’s disease such as memory loss, behavioral changes, and loss of bodily functions also worsen with age. Current treatments are unable to stop or reverse the progression of impairment. A major roadblock to effective treatment is our inability to disentangle how many age-related processes contribute to the onset and progression of Alzheimer’s disease. Understanding the interconnectedness of different biological processes and their role in manifesting symptoms is essential for designing and choosing effective treatments.

The Zwang lab approaches this problem by studying how neurons and their circuits change with age and Alzheimer’s disease. Our goal is to determine which features of Alzheimer’s disease cause neurodegeneration, understand the trajectory of changes that arise as a result, and separate causal from coincidental features. To do this, we develop and apply methods with exceptional spatiotemporal resolution.  This includes the use of flexible bioelectronics that can record changes in brain activity as pathology develops over months, virtual reality systems to test how behavioral responses to stimuli changes over time, multiphoton microscopy to visualize the degeneration of neural structures over time, and lightsheet imaging to characterize the organization and influence of pathology across brain regions.