As research into Alzheimer’s advances, scientists are shifting their focus from beta-amyloid accumulation to inflammation as a main driver of the disease. In a new study, researchers at the University of California, Irvine discovered that a protein known as TOM-1 plays a role in inflammation associated with Alzheimer’s disease.
“Scientists have known for a long time that inflammation is a driver of Alzheimer’s disease, but inflammation is complex and involves many factors,” Frank LaFerla, Dean of the School of Biological Sciences at the University of California, said in a press release. “That’s why we decided to look at TOM-1.”
TOM-1 and Inflammation
In the study, the researchers honed in on TOM-1’s link to inflammation in the brain.
“We were interested in TOM-1 because its levels are low in the Alzheimer’s brain and in the brains of Alzheimer’s rodent models,” Alessandra Martini, a postdoctoral researcher and author of the study, said in the press release. “However, its specific role in the disease has largely been unexplored.”
The study found that when TOM-1 levels were decreased in rodents, the animals experienced a rise in Alzheimer’s pathology—such as an increase in beta-amyloid buildup, inflammation and cognitive impairment—while boosting TOM-1 levels actually reversed these negative effects.
“[Reducing TOM1] worsens inflammation, impairs microglial phagocytosis, and significantly exacerbates amyloid deposition,” the authors wrote in the study. “Conversely, restoration of TOM1 reverses these effects and reduces amyloid-beta pathology. These results highlight the importance of endosomal adaptors and their interaction with inflammatory receptors in the pathogenesis of Alzheimer’s disease.”
Inflammation’s Role in Alzheimer’s
Brain inflammation, or neuroinflammation, can be a complicated topic. In many ways, inflammation works as a good force that helps clean the brain. Microglia, cells involved in the central nervous system’s immune response, scavenge and clear damaging elements like toxic proteins from the brain. They also release cytokines, pro-inflammatory molecules. In Alzheimer’s, however, this inflammatory response is over-activated and can become harmful.
“Inflammation is normally a ‘good guy.’ It clears infections and helps heal wounds, for example,” Linda Van Eldik, director of the Sanders-Brown Center on Aging at the University of Kentucky, told Being Patient in a past interview. “But in Alzheimer’s disease, the inflammation somehow gets out of whack. It gets too strong and sustains for too long—it’s now turned into a ‘bad guy,’ destroying the neurons that carry signals from one part of the brain to the next.”
While most Alzheimer’s drugs in development have focused on reducing beta-amyloid, more researchers are beginning to design therapeutic interventions that can fight inflammation.
The researchers of the latest study believe that TOM-1 may hold some answers to stopping inflammation as researchers continue to search for new therapeutic routes.
“You can think of TOM-1 as being like the brakes of a car and the brakes aren’t working for people with Alzheimer’s,” LaFerla said in the press release. “This research shows that fixing the brakes at the molecular level could provide an entirely new therapeutic avenue. With millions of people affected by Alzheimer’s and the numbers growing, we must research a diverse portfolio of approaches so we can one day vanquish this terrible disease.”