Find all causes of Alzheimer's disease and a cure

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.”

The microbiome is the population of microorganisms-such as bacteria, fungi, viruses, protozoa, and others-that exist in humans, each of which may have a helpful or a harmful role. Our bodies contain more than 10 times the number of microbial cells than they do human cells. The largest population of microbes exists in the intestinal tract, thought of by some as the largest immune organ in the body. Intriguing research from across neurological diseases has raised the possibility that some microbes in the gut can modify the production of chemicals occurring in the brain. Cure Alzheimer’s Fund researchers are investigating whether the microbiome may impact the progression of early Alzheimer’s disease pathology.

More than a century ago, the Nobel laureate Elie Metchnikoff postulated that ‘good gut bacteria’ may delay senility and have beneficial effects for the symptoms of anxiety and depression associated with deteriorating cognition. Manipulation of the gut microbiome has since become common practice with widespread consumption of probiotics. While the broad array of health benefits claimed for probiotics has failed to be substantiated in controlled clinical studies, findings have shown that the gut microbiome is essential for normal brain function.

Signal molecules from the microbiome can enter the central nervous system and modulate brain activities, sometimes producing profound effects in animal models. Recent revelations regarding Alzheimer’s disease show that there exists a two-way communication system between the microbiome and brain. Findings suggest that under disease conditions, the “back-and-forth” between the brain and microbiome may become disrupted and reinforce harmful pathways that promote pathology. Abnormal brain activity can shift conditions in the gut and lead to a rise in gut bacteria linked to neuroinflammation and poor health outcomes. Change in the gut microbiome lead, in turn, to increases in metabolites that exacerbate neuroinflammation, anxiety, and depression in the brain. It is not be surprising to learn that brain health is intricately linked to the state of the rest of the body.