Understanding the immune system in Parkinson’s

Research into immune responses in Parkinson’s has focused primarily on the brain’s resident immune cells, microglia, but more recently, a number of studies have shown that both the innate and the adaptive immune system may also be involved in driving the disease and different symptoms.

Understanding how the immune system and mechanisms in the periphery interact with the brain is an important part of the puzzle and may yield promising targets for disease modification.

Efforts to understand immune responses in Parkinson’s have been ongoing for several years. Initially, microglia, these non-neuronal cells which nonetheless play an essential role in defending neurons from pathogens, were the main point of focus. Researchers were finding that they were elevated in the brains of people with Parkinson’s, as a result of coming in contact with misfolded alpha-synuclein and unhealthy cells. However, increasing evidence now points to the fact that other parts of the immune system around the body get activated quite early on in the progression of the disease as well.

Higher levels of particular kinds of immune cell and their particular form and function were found when analyzing blood samples from people with Parkinson’s. In addition, their function appears to be subtly changed: for example, one study found that specific molecules regulating interactions between the brain and immune cells circulating around the body were deranged in a way that meant that they were less effective at dampening inflammation when this was no longer needed. Not only is this and other aspects of the innate immune system altered in Parkinson’s, but changes in the adaptive immune system which responds to environmental threats and creates so called immune memory have also been documented. This article reviews a number of studies aiming to understand these changes.

Although there is no single immune marker that can be monitored as a direct and specific tracker of Parkinson’s progression, this continually growing body of work may deliver new and important insights which the authors predict may rely on the combination of several different markers. Another point of focus have been the effects of different kinds of infection, for example through viruses like the flu, and bacteria such as H Pylori, a major cause of stomach ulcers which is now easily eradicated through a regimen of antibiotics and acid reducing medication. These seem to show some potentially interesting associations with Parkinson’s risk.

Some of this work is translating tangibly into vaccines which are being trialed for Parkinson’s More generally, inflammation and immune responses are now considered an important part of the puzzle. Watch this space!

PIPELINE REVIEW

Parkinson’s Movement – Immunotherapies BIIB054