MIT To Model Alzheimer’s Disease
MIT is all set to model Alzheimer’s disease complexity on a chip
Due to the complexity of Alzheimer’s disease, it has been challenging for researchers to recreate the condition in the lab. Alzheimer’s affects many types of cells in the brain, including its blood vessels.
With a new 5.6 million dollar, five-year grant from the National Institutes of Health (NIH), MIT neuroscientists at The Picower Institute for Learning and Memory will develop an integrated “brain-on-a-chip.” This will be done to model the disease’s complexity with novel technologies. This will provide a powerful tool for personalized disease and treatment.
The lab of Picower Professor Li-Huei Tsai will develop its miBrain-chip platform. It will start from a crucial component that Alzheimer’s models typically omit- blood vessels that replicate the function of the blood-brain barrier, which stringently filters the material that enters or leaves the brain through the circulatory system.
Tsai lab postdoc- Joel Blanchard successfully engineered and validated such an in vitro blood-brain barrier (BBB) from patient-derived stem cells. He was also successful in makin
g a version with the Alzheimer’s risk gene variant APOE4. It showed that it recapitulates the same vascular problems, like cerebral amyloid angiopathy, seen in Alzheimer’s patients.In collaboration with the lab of Robert Langer, David H. Koch Institute Professor in the Departments of Chemical Engineering and Biological Engineering and the Koch Institute at MIT, Tsai and Blanchard will integrate the blood-brain barrier (BBB) into a chip system including the primary cell types of neurons, microglia immune cells, and oligodendrocytes. These maintain the efficiency of neural circuits through a process called myelination. The brain’s immune response and myelination both appear to be compromised by Alzheimer’s disease.
Blanchard said that this new model includes most of the cell types of the human brain. Henceforth, it will provide insight into how they interact and how those interactions change during the progression of Alzheimer’s.
In the first two years of the research, the team will develop and validate the chip platform’s ability to replicate both healthy and diseased states. If that’s successful, researchers will then begin to use it for different kinds of experiments.
According to the idea proposed in the grant, the team will make miBrain-chips from tissue samples of patients who lived with Alzheimer’s disease and a group of healthy individuals without any condition of Alzheimer’s. They will work with Professor Manolis Kellis from MIT’s Computer Science Department to build computational models that track changes in cell dynamics, gene expression, and other crucial data. With this technique, researchers can track and analyze the disease progression in the chip system. After that, they will compare it to related data in the individuals’ medical histories. Researchers can also examine the effects of potential treatment interventions in copies of those systems and track their impact.
According to the grant abstract, this study will yield insight into Alzheimer’s disease development. It will also create a platform for discovery and efficacy screening of therapeutics.
The system, once developed, would allow for other similar experiments, which will help in personalized and better treatment.
