From the WUSTL Newsroom…
Scientists studying the way Alzheimer’s takes root in the brain have identified important new similarities between a mouse model and human Alzheimer’s.
Researchers at Washington University School of Medicine in St. Louis have shown that brain plaques in mice are associated with disruption of the ability of brain regions to network with each other. This decline parallels earlier results from human studies, suggesting that what scientists learn about Alzheimer’s effects on brain networks in the mice likely will be transferable to human disease research.
The study, published in the Journal of Neuroscience, is among the first to precisely quantify the effects of Alzheimer’s disease plaques on brain networks in an animal model. Until now, scientists studying Alzheimer’s in animals have generally been limited to assessments of structural brain damage and analyses of brain cell activity levels.
“Precise measurement of changes in brain networks are critical to understanding Alzheimer’s and will likely be important in models of other neurodegenerative disorders,” says senior author David M. Holtzman, MD, the Andrew B. and Gretchen P. Jones Professor and head of the Department of Neurology. “For example, we can now test whether blocking Alzheimer’s plaques from building up in the mouse brain prevents disruptions in brain networks.”
In humans, scientists assess the integrity of brain networks by monitoring cerebral blood flow with functional magnetic resonance imaging scans. When the brain is idle, blood flow rises and falls in sync in brain regions that network with each other, a phenomenon called functional connectivity. These links are believed to be an important component of normal brain activity. In humans, problems in functional connectivity appear to presage the development of dementia.
Applying the same technique to mice can be very challenging, Holtzman says. Instead, researchers used an approach for monitoring brain blood flow in mice recently developed by the laboratory of Joseph Culver, PhD, associate professor of radiology at Washington University. The technique involves mounting a ring with light-emitting diodes on the head of a lightly anesthetized mouse. Sensors in the ring monitor light that is reflected back from hemoglobin molecules flowing through blood vessels in the brain. This data can be used to quickly assess blood flow.
Researchers applied the approach to a mouse model of Alzheimer’s disease. They found that the brain regions with the strongest network connections in young mice developed the most plaques as the mice aged. As plaques accumulated in these regions, functional connectivity declined. Scientists have already found similar results in humans using functional magnetic resonance imaging.
For more from Michael C. Purdy of the WUSTL Newsroom, click here.