Scientists in Australia have come up with a unified hypothesis for the etiology of dementia, Alzheimer’s, and other neurodegenerative diseases—these conditions are all caused by an immune response of the innate surveillance system, which leads to a progressively expanding cascade of inflammation, tissue damage, and cell death.
“There is now decisive evidence supporting the hypothesis that innate surveillance-mediated cell death is a common cause, not simply a consequence, of nerve cell death and therefore the principle causal mechanism of neurodegenerative disease,” the authors wrote in an article published online May 10, 2016 in the journal Frontiers in Neuroscience.
Alzheimer’s researchers continue to investigate the role of amyloid plaques and tau proteins in the brains of affected patients, but it is well known that these deposits don’t fully explain the cause of Alzheimer’s disease.
“Remarkably, neurodegenerative diseases are increasingly found to be accompanied by activation of the innate immune surveillance system normally associated with pathogen recognition and response,” the authors wrote. “Innate surveillance is the cell’s quality control system for the purpose of detecting such danger signals and responding in an appropriate manner.”
The innate immune system is ancient, the researchers described, and plays a defensive role in all classes of plants and animals. It provides immediate defense against pathogens and other invaders.
“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 the study’s lead author Robert Richards, PhD, Professor and Head of Genetics and Evolution at the University of Adelaide’s School of Biological Sciences, in Adelaide, Australia.
“Remarkably, researchers from other laboratories were, at the same time, reporting similar features in other neurodegenerative diseases,” Dr. Richards explained. “When we pulled the evidence together, it made a very strong case that uncontrolled innate immunity is indeed the common cause.”
Although this hypothesis provides one answer, it also raises many questions, such as why some individuals are more susceptible to neurodegeneration than others at different stages of life.
The answer to this may lie in intrinsic errors in the innate immune system itself, the researchers explained. That is, the innate immune system may interpret that certain genetic mutations or particular responses to environmental factors are “danger” signals—each one contributing to the cumulative risk of neurodegeneration.
“Many of the genetic changes linked with neurodegeneration can be demonstrated to specifically escalate the innate surveillance pathway,” the authors wrote.
Dr. Richards added, “We hope this new way of understanding neurodegeneration will lead to new treatments. 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.”