A definitive feature of Alzheimer’s disease is the presence of senile plaques, the sticky conglomerates of the beta-amyloid protein which appear in the brain of affected individuals and are thought to play a key role in brain dysfunction. However, one of the biggest controversies in studying Alzheimer’s is that these plaques do not correlate with dementia in humans, and therefore some early role of beta-amyloid is thought to initiate neuron damage.

The Bacskai lab seeks to determine exactly how beta-amyloid interferes with cell function in the brain, using multiphoton imaging approaches to visualize the plaques in brains of living mice. This can be accomplished by using transgenic mice that overexpress mutant human genes leading to a model of amyloid production and aggregation.  By selectively targeting and labeling all of the cell types in the brain (neurons, astrocytes, microglia, smooth muscle cells, oligodendrocytes, etc) with structural and functional imaging probes, we can see what happens to these specific cell types over periods of many months.  Additionally, this platform can be used to evaluate drug treatments with real time imaging before and during therapy.

The development of novel optical techniques is ongoing in our lab, and includes methods to measure protein-protein interactions using fluorescence lifetime imaging microscopy (FLIM), adaptive optics, high speed volumetric imaging, light sheet microscopy, and non-invasive approaches with near infrared imaging in intact animals.