For decades, Alzheimer’s disease research has focused on neurons. That’s logical: after all, it’s our brain cells that become diseased, causing a decline in our memory and ability to think. But new research from Li-Huei Tsai’s lab suggests the immune system may also play a role in Alzheimer’s.
The discovery is welcome news since, so far, clinical trials of Alzheimer’s drugs that target neurons have been unsuccessful. “We really need a portfolio of targets,” says Tsai, Picower Professor of Neuroscience and Director of the Picower Institute of Learning and Memory.
About 35 million people worldwide have dementia. More than 5 million Americans have Alzheimer’s disease. And the numbers are expected to rise in the coming decades as the population ages. Also, because there are no effective therapies for these diseases, the costs of care are high. In fact, in the US, the cost of Alzheimer’s disease care exceeds all other health care costs.
“If we don’t address the need for treatment now, the economic burden is going to be unbearable soon,” says Tsai, who is taking on this challenge.
Tsai is leading the Aging Brain Initiative. This collaborative effort at MIT focuses on brain aging because it is a risk factor that spans all forms of dementia, but how it influences these diseases is unknown. “We still don’t quite understand how dementia begins and progresses,” says Tsai. “This contributes to the fact that we don’t have a whole lot of options when it comes to drugs.”
The Aging Brain Initiative brings together an accomplished group of MIT researchers, including neuroscientists, biologists, computer scientists, and engineers, to leverage MIT’s strengths to build foundational brain-aging knowledge and rapidly bring solutions to the clinic. The Initiative’s four-pronged approach will identify aging biomarkers, develop circuit-specific therapeutics, explore personalized molecular medicine, and identify strategies to promote healthy brain aging.
Other founding members include: Edward Boyden, associate professor of Biological Engineering and Brain and Cognitive Sciences; Emery Brown, Edward Hood Taplin Professor of Medical Engineering and of Computational Neuroscience; Leonard Guarente, Novartis Professor of Biology; Robert Horvitz, David H. Koch Professor of Biology; Susan Lindquist, Professor of Biology; and Susumu Tonegawa, Picower Professor of Biology and Neuroscience.
Tsai is also co-associate director of the new Paul F. Glenn Center for Science of Aging Research at MIT, which will leverage the strengths of MIT biologists, neuroscientists, and cancer researchers to understand aging.
Tsai’s discovery that the immune system may play a role in Alzheimer’s disease is an example of how fundamental research can drive new ideas for clinical therapies. The team investigated brain epigenetics, changes in cellular interactions with DNA that redirect gene behavior. This work led to the discovery of misbehaving immune cells in the brains of mice engineered to mimic Alzheimer’s. “Now we realize the immune system plays an important role, and possibly a causative role in Alzheimer’s disease,” she says.
Tsai is already acting on these findings, which were published in Nature last winter. One effort is sharply focused on screening for drugs that might correct immune cell behavior.
Another effort, in collaboration with the Broad Institute, will look at the individual gene expression profiles of a wide range of immune cells. This analysis, called single-cell RNA sequencing, will provide Tsai with an extraordinarily detailed view of how many different types of immune cells there are in the brain. “There’s a sense that there are beneficial immune cells and bad immune cells in the brain,” she says. “So we say, how many different kinds are there? We need to get to know them better before we know the best way forward.”
The Aging Brain Initiative aims to undertake a portfolio of these types of collaborative projects, to foster rapid progress of discoveries into clinical medicine, and to move forward as a large consortium-like team.