Research and treatment efforts for Alzheimer’s disease have traditionally focused on what happens in the brain. But there has recently been a growing body of evidence that what happens elsewhere in the body—such as the microbial population of the gut—could play a key role in the disease as well.

A new project led by Massachusetts General Hospital's Deepak Vijaya Kumar, PhD, and supported by the non-profit Cure Alzheimer's Fund will work to untangle these connections with the hope of finding new strategies for diagnosis and treatment.

Building on a Game Changing Insight

Kumar's research is an extension of a key scientific insight that came out of the Genetics Research and Aging Unit at Mass General several years ago.

In a 2016 study, a team led by Robert D. Moir, PhD, and Rudolph E. Tanzi, PhD, demonstrated that amyloid beta—long thought to function solely as a harmful byproduct of Alzheimer’s disease—actually plays a protective role by entrapping microbes that cross the blood-brain barrier to stop them from harming the brain.

Other connections between the microbiome and Alzheimer's disease have been uncovered as well. Researchers have previously shown that AD mice (mouse models of Alzheimer’s disease genetically engineered to develop the hallmark plaques and tangles of the disease) also develop a different balance of bacteria in the gut than healthy mice.

Scientists have also demonstrated AD mice raised in a sterile environment, with little or no microbes in their intestines, had significantly lower doses of amyloid in the brain and did not develop plaques.

A Promising New Model of the Disease

Kumar will now investigate how changes to bacteria in the gut affect disease progression in a new mouse model—one that is bioengineered to produce the amyloid protein, but not genetically destined to develop—plaques and tangles.

"If these mice have a lot of amyloid beta in the brain in a soluble form, is it possible to manipulate the gut ecosystem and make them develop plaques? That’s going to be the challenge."

Insights into how bacterial changes in the gut correlate with Alzheimer’s disease could help with earlier disease diagnosis—it may be that these changes occur before individuals start experiencing cognitive issues such as memory loss.

It could also point to new treatment strategies that indirectly slow or halt the progression of plaques and tangles in the brain by restoring a healthy microbial population to the gut.

Could Fecal Transplants Help?

One of the most effective strategies for restoring balance to an unbalanced gut microbiome is through fecal microbiota transplant (FMTs)—essentially transplanting fecal material from a healthy intestine into an unhealthy one.

While the process may not sound too appealing, fecal transplants have already been successful in treating some human intestinal infections caused by Clostridium difficile.

Kumar will also use the new mouse model to test FMTs as a treatment. If it is possible to make plaques and tangles form in the brain by altering the gut microbiome in these mice, is it possible to halt or slow that same process by returning it back to normal?

Kumar has created a new term to describe his unique niche in the research world at the intersection of neurology and microbiology—neuromicrobiology.

"I think this is the best field I could be in." he says. "It's exciting because you are looking at the problem from two different angles at the same time."

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