For decades, researchers have studied Alzheimer’s disease searching for the causes that lead to the pathology and the eventual breakdown in cognitive ability for those who are affected. Replicating the disease in the lab was extraordinarily difficult using standard laboratory models.
Through a grant provided in 2014 by Cure Alzheimer’s Fund, Rudolph Tanzi, Ph.D., and Doo Yeon Kim, Ph.D., of Massachusetts General Hospital created a new model called Alzheimer’s in a Dish.
“Previous attempts at growing human brain cells in the lab and inducing them to form the plaques and tangles characteristic of Alzheimer’s disease were performed in a two-dimensional Petri dish system. And, in this flat, 2-D environment, plaques and tangles simply didn’t appear,” said Dr. Francis Collins, director of the National Institutes of Health and leader of the Human Genome Project, in a 2014 blog post.\
Kim had suggested growing human neural stem cells in a gel medium. The gel system allowed the cells to grow in a more natural 3-dimensional form.
This discovery caught the attention of researchers as well as the science media. In an October 2014 story, The New York Times wrote, “For the first time, and to the astonishment of many of their colleagues, researchers created what they call Alzheimer’s in a Dish—a petri dish with human brain cells that develop the telltale structures of Alzheimer’s disease. In doing so, they resolved a longstanding problem of how to study Alzheimer’s and search for drugs to treat it; the best they had until now were mice that developed an imperfect form of the disease.”
The article went on. “Of course, a petri dish is not a brain, and the petri dish system lacks certain crucial components, like immune system cells, that appear to contribute to the devastation once Alzheimer’s gets started. But it allows researchers to quickly, cheaply, and easily test drugs that might stop the process in the first place.”
For their work, Tanzi and Kim received the Smithsonian Ingenuity Award.
Now Tanzi and Kim, and Hansang Cho, Ph.D., of the University of North Carolina, Charlotte, have taken the model to a new and more comprehensive dimension.
Tanzi explains, “Our original ‘Alzheimer’s in a Dish’ system recapitulated the plaques and tangles typically seen in the brains of patients with Alzheimer’s disease, but did not induce neuroinflammation. Studies have shown that we can have many plaques and tangles in our brains with no symptoms, but when neuroinflammation kicks in, exponentially more neurons die and cognitive impairment leading to dementia is induced. A complete model of Alzheimer’s pathology needs to incorporate that ‘third leg of the stool.’”
Newsweek reported on the advancements in its August 2018 edition.
“This set-up provided an effective environment for the researchers to model the kind of neuroinflammation seen in Alzheimer’s using human brain stem cells that had been modified to have a genetic disposition to the disease. Promisingly, with the help of their model, the team found that by blocking two receptors in microglial cells—glial cells that function as nervous system cells—they could prevent neuroinflammation, opening up new opportunities for the discovery of novel drugs.”