A molecule involved in the brain’s mechanism for resolving inflammation might stave off memory loss in Alzheimer’s disease, a study in mice suggests.
Inflammation is a normal part of the immune system’s response to harmful stimuli, such as pathogens and toxins.
Once the body has neutralized the threat, it deploys specialized molecules that resolve the inflammation.
However, this inflammation-resolving mechanism can fail, resulting in chronic inflammation. This has implications in a wide range of illnesses, including heart disease, asthma, rheumatoid arthritis, and Alzheimer’s disease.
Alzheimer’s may affect as many as 5.5 million people in the United States and millions more around the world.
The condition is a progressive, irreversible brain disorder that reduces memory and cognitive skills over many years.
A new study raises the prospect that by damping down inflammation, a molecule that is part of the brain’s inflammation-resolving mechanism called RvE1 (short for Resolvin E1) could prevent memory loss in individuals with Down syndrome and similarly in Alzheimer’s disease.
The study is now available in the journal GLIA.
A team of researchers led by Eric D. Hamlett, Ph.D., assistant professor in the Department of Pathology and Laboratory Medicine at the Medical University of South Carolina, found that RvE1 worked well in a mouse model of Down syndrome.
They chose this particular disease model because inflammation of the brain starts early in the lives of people with Down syndrome. This may partly explain why their risk of developing Alzheimer’s is nearly 80% by the age of 60.
The scientists implanted a tiny pump under the skin of each mouse. Over the space of 4 weeks, the pump delivered a steady stream of RvE1 dissolved in saline solution to some mice. The pump delivered saline alone to a control group.
Behavioral tests revealed that the mice dosed with RvE1 had significantly less memory loss over this period than the control mice.
They also had lower levels of molecules called cytokines circulating in their blood, which accompany inflammation.
In addition, there was evidence that inflammatory immune cells called microglia were less active in the mice’s hippocampus, a part of the brain closely involved in learning and memory.
RvE1 did not seem to cause any adverse side effects in the mice.
Dr. Hamlett collaborated with researchers from the Center for Alzheimer’s Research at the Karolinska Institute in Sweden, and the Knoebel Institute for Healthy Aging at the University of Denver, CO.
“Our bodies first need to be able to respond to a problem and then have a separate and equally important response to resolve the inflammation mechanism […] In our model, we can now engage this response with the specialized lipids and, in a more natural way, calm down long-term inflammation.”
– Eric D. Hamlett, Ph.D., University of South Carolina
In their paper, the scientists write that their work could lead to preclinical tests of RvE1 as a treatment for preventing the memory loss associated with Alzheimer’s disease.
They note that a study in 2014 showed that RvE1 could reduce inflammation elsewhere in the body, prompting a clinical trial of the molecule for treating peripheral inflammatory conditions.
Their own study has demonstrated that RvE1 can cross the blood-brain barrier, which means it may have the potential to tackle inflammation inside the brain, too.
One significant limitation of their study is that the effects of RvE1 in mice may not accurately reflect how the molecule affects brain inflammation in people with Alzheimer’s.
For example, protein tangles accumulate in the brains of humans with Alzheimer’s, which in turn may contribute to chronic inflammation.
But these tangles did not develop in the brains of the mice models used in this study.