Imaging damaged brain cells in mice provides clues into Alzheimer’s disease

Using recently developed techniques for imaging individual cells in living animals, School of Medicine researchers have watched as Alzheimer’s-like brain plaques damage mouse brain cells.

“We’ve been able to visualize damaged nerve connections in living animals and follow them over time in the same animal,” said principal investigator David M. Holtzman, M.D. “Our next step is to determine whether such damage is reversible.”

Holtzman is the Andrew B. and Gretchen P. Jones Professor of Neurology and head of the Department of Neurology, the Charlotte and Paul Hagemann Professor of Neurology and a professor of molecular biology and pharmacology. The first author of the study is Robert P. Brendza, Ph.D., research instructor in neurology.

In the 1990s, biologists discovered the protein that makes certain jellyfish luminescent also could be used to generate fluorescent cells in other species. By shining light on a living mouse engineered to contain these proteins, researchers can watch cellular activity over time using a sophisticated multiphoton microscope.

Holtzman’s team used this technique to examine the brains of mice that develop plaques similar to those characteristic of Alzheimer’s disease. The mice also were engineered to have a subset of neurons express yellow fluorescent protein. Using this model, the scientists observed neurons becoming increasingly disrupted by brain plaques over time.

“We plan to use this system to further examine the process of nerve cell damage and degeneration,” Holtzman said.

“This line of research should provide new insight into the underlying processes involved in the development of Alzheimer’s disease and help us determine whether the proteins that accumulate as brain plaques are a useful and feasible target for Alzheimer’s therapies.”

The study was conducted in collaboration with researchers at Massachusetts General Institute for Neurodegenerative Disorders, Harvard Medical School, the University of Pittsburgh and Eli Lilly and Co.

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