A new imaging study has found neuroinflammation may be more common in neurodegenerative diseases than previously suspected. The Cambridge research revealed brain inflammation to be a common thread across three different types of dementia.
Obviously inflammation isn’t inherently a bad thing. In a healthy body signs of inflammation point to a functional immune system fighting off a pathogen or healing a wound. Sometimes a person’s immune system doesn’t work correctly and mistakenly attacks healthy cells and tissue. This is classically known as an autoimmune disease, manifesting in conditions such as arthritis.
Over the last couple of decades researchers have started implicating inflammation as playing a role in a number of conditions not traditionally thought of as autoimmune diseases, particularly in reference to the brain. Depression, Alzheimer’s disease, and even suicidal thoughts have all been recently linked to neuroinflammation, and although no causal connections have been established so far, the associations detected are significant.
In this new study, published in the journal Brain, researchers scanned the brains of 31 subjects with three very different types of frontotemporal dementia (FTD). These different kinds of dementia all present different clinical and pathological signs, however, the aggregation of specific toxic proteins in damaged areas of the brain is one unifying factor.
All the subjects in the study underwent two kinds of Positron Emission Tomography (PET) scan. One scan to highlight neuroinflammation, and another scan to illuminate the toxic proteins known to be linked with neurodegeneration.
"We predicted the link between inflammation in the brain and the build-up of damaging proteins, but even we were surprised by how tightly these two problems mapped on to each other," says Thomas Cope, one of the authors on the new study.
The big question that now remains is what role this neuroinflammation plays in the neurodegeneration associated with dementia.
A secondary study examining 12 post-mortem brains found similar patterns between toxic protein build-up and neuroinflammation. This suggests the relationship between neuroinflammation and toxic proteins is present throughout the course of the disease.
The big question that now remains is what role this neuroinflammation plays in the neurodegeneration associated with dementia. Is the inflammation causing its own degenerative damage, or is its presence merely a consequence of the aggregation of toxic proteins?
“Microglia play a key role in orchestrating the innate immune response of the brain,” the researchers write in the study. “They can be activated by misfolded proteins, and mediate responses through inflammatory pathways, cytotoxicity and changes in plasticity. In neurodegenerative diseases, this state of activation may become chronic, dysfunctional, and toxic, contributing to pathogenicity.”
The study makes no claims to neuroinflammation playing a causal role in dementia. Instead, all it establishes is a strong relationship between inflammation and disease progression across different kinds of FTD.
The researchers do note the importance of further study investigating the effect of neuroinflammation at the early stages of neurodegeneration. If a mechanistic link between toxic protein aggregation and inflammation can be uncovered then a number of new treatment pathways could open up to scientists.
“The illnesses are in other ways very different from each other, but we have found a role for inflammation in all of them," explains James Rowe, one of the researchers working on the study. "This, together with the fact that it is known to play a role in Alzheimer's, suggests that inflammation is part of many other neurodegenerative diseases, including Parkinson's disease and Huntington's disease. This offers hope that immune-based treatments might help slow or prevent these conditions."
The new study was published in the journal Brain.
Source: University of Cambridge