Dementia and other neurodegenerative diseases may be symptoms of inflammation caused by an out-of-control immune system, according to researchers at the University of Adelaide in Australia.
Previously, most dementia and Alzheimer’s research has focused on the role of protein deposits called amyloid plaques that lodge in the brains of patients with Alzheimer’s. But it is becoming increasingly clear that this is an inadequate explanation for the disease.
The investigators have gathered very strong evidence showing that the neurological decline found in dementia-related diseases is triggered by “auto-inflammation,” a phenomenon in which the body’s own immune system develops a persistent inflammatory response leading to brain cell death.
Neurodegeneration comes in many different forms, including Alzheimer’s, Parkinson’s, and Huntington’s Diseases. These conditions are differentiated by their initial symptoms as well as by the various types of brain nerve cells that are first affected. However, as all of these diseases progress, they become more and more similar. The researchers believe that each disease may actually have the same underlying mechanism and share a common pathway of nerve cell loss.
“Our interest in the body’s own (innate) immune system as the culprit began when we discovered that immune system agents become activated in a laboratory model of Huntington’s Disease,” says study lead Professor Robert Richards from the University of Adelaide’s School of Biological Sciences.
“Remarkably, researchers from other laboratories were at the same time reporting similar features in other neurodegenerative diseases. When we pulled the evidence together, it made a very strong case that uncontrolled innate immunity is indeed the common cause.”
The innate immune system, which is the cells’ first line of defense, is normally able to distinguish the body’s molecules from foreign, disease-causing molecules. It is an alarm and response system with a self-destruct mechanism to contain and eliminate invaders or abnormal cells, such as cancer.
Problems can arise due to a variety of triggers including genetic mutations, infection, toxins, or physical injury, all of which have been linked with different forms of neurodegeneration. Initially the innate immune system protects the tissue against these triggers, but prolonged activation becomes self-perpetuating, causing brain cell death to occur.
“We hope this new way of understanding neurodegeneration will lead to new treatments,” Richards says. “We now need to further investigate the immune signaling molecules, to identify new drug targets that will delay the onset and/or halt the progression of these devastating diseases.”
“Dementia, including the most common form Alzheimer’s Disease, and related neurodegenerative conditions are dramatically rising in frequency as people live longer and our population ages,” says Richards.
“Australia is predicting that by 2050 there will be almost double the number of people with dementia, and the United States similarly says there will be twice as many. Currently we have no effective treatments to assist the millions of affected people, and these diseases are an enormous burden on families and the public health care system.”
The findings are published in the journal Frontiers in Neuroscience.
Source: University of Adelaide