As part of its ongoing research to better understand the complexities of the human brain, the Allen Institute for Brain Science, Seattle, USA, is embarking on the first effort to map connectivity patterns across the whole brain in mouse models of Alzheimer’s disease, through its recent award of a US$3.4 million grant over five years from the National Institute on Aging of the National Institutes of Health.
“Many studies on Alzheimer’s disease focus on just one or a small number of areas in the brain, such as the hippocampus, for its role in memory,” says Julie Harris, assistant investigator at the Allen Institute for Brain Science and primary investigator on the grant. “By studying connections across the entire cortex in both normal mice and mouse models of the disease, we hope to finally make the breakthroughs that will help us understand the pathways through which Alzheimer’s disease spreads, and what interventions we can make against its progression.”
So far, clinical trials for drugs developed in mouse models that typically focus on individual brain areas have yielded poor results. “Our expanded view of the disease that looks at connections across the whole brain will hopefully improve mouse models and their use in translational research to identify drugs and treatments that work in humans,” says Harris.
The whole-brain model of Alzheimer’s builds on the Allen Mouse Brain Connectivity Atlas, recently profiled in the journal Nature, which allows researchers to quantitatively analyse connections across the entire mouse brain.
Harris and her colleagues plan to expand the resource by focusing on areas of the brain that are hardest hit early in the disease. They will work backwards first, using viral tracers to discover which regions of the brain send their neurons to those hard-hit areas. Then, they will follow the other projections from those source regions to different parts of the brain, ultimately creating a detailed map showing how and which brain regions are interconnected, and how these connections are altered by disease. In the spirit of other Allen Institute resources, they plan to make the data publicly available through the Allen Brain Atlas data portal.
