Chronically Active Innate Immune System Seen as Likely Cause of Dementia in Alzheimer’s Patients

Chronic activation of the innate immune system is the main cause of a range of symptoms common to different neurodegenerative diseases, namely dementia, which is often associated with Alzheimer’s disease, researchers at the University of Adelaide reported. Their study, titled “The Enemy within: Innate Surveillance-Mediated Cell Death, the Common Mechanism of Neurodegenerative Disease,” was published in Frontiers in Neuroscience.

Neurodegenerative diseases, such as Alzheimer’s, Parkinson’s and Huntington’s, are all characterized by the selective death of neurons in the central nervous system. Evidence has shown that such neurodegeneration is accompanied by the activation of the innate immune system, which possibly launches an over-the-top response that culminates in abnormal cell death.

“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,” Professor Robert Richards, the study’s lead author, said in a news release. “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.”

Researchers analyzed evidence investigating cell death, neurodegeneration, and symptoms such as dementia. The innate surveillance system, essential for the detection and elimination of a pathogen attack, is composed of intracellular, extracellular, and systemic responses. Repeat studies have shown that mutations in proteins involved in this immune response are linked to many familial forms of neurodegenerative diseases, suggesting that those harboring these mutations have amplified inflammatory responses, and that consequent cell death and tissue damage are possible pathways responsible for these diseases.

Factors such as infection, toxins and physical injury can also lead to a dysfunctional immune system. The innate immune system initially protects against these triggers, but prolonged activation becomes self-perpetuating, causing brain cell death.

Investigators hope that this unifying view of neurodegenerative diseases will lead to new  research and improve the design of clinical trials.

“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,” said Professor Richards. “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.”