Inflammation elevated in brains of newly diagnosed patients

Study suggests such inflammation may be early driver, not byproduct, of disease

Marisa Wexler, MS avatar

by Marisa Wexler, MS |

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A person with a microphone speaks, while a person wearing a lab coat shines a light onto an oversized brain with tissue that is floating between them.

Inflammation in the brain is detectable at the earliest stages of Parkinson’s disease and even before treatment is begun, a new study reports.

The findings support the idea that inflammation may be an early driver of Parkinson’s itself, rather than merely a byproduct of the disease’s neurodegeneration, the researchers noted.

“An association between inflammation and Parkinson’s is well known, but a fundamental question remains unanswered: Does inflammation play a role in the onset of Parkinson’s, or is it a byproduct of the disease itself?” Talene Yacoubian, MD, PhD, a professor at the University of Alabama at Birmingham (UAB), said in a university press release. “Our findings show that inflammation is present in the early stages of the disease.”

The study, “Brain and Systemic Inflammation in De Novo Parkinson’s Disease,” was published in Movement Disorders.

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Increased inflammation in the brain is a well-established feature of Parkinson’s and many other neurological disorders. However, an important question remains largely unanswered: Does inflammation drive Parkinson’s disease, or is it the other way around?

One of the major obstacles in addressing this question, the researchers noted, is that studies assessing brain inflammation in Parkinson’s often include people with a wide range of disease severity and duration and who already are on medications that may alter inflammatory status.

In this study, Yacoubian and colleagues at UAB conducted clinical and imaging evaluations of 58 people (33 men and 25 women) who had been diagnosed with Parkinson’s less than two years prior and had not yet begun treatment. Their mean age was 66.1 years.

“Enrolling study subjects early in their disease progression was significant. We wanted to see if inflammation was present early on in the disease, before patients had even begun on Parkinson’s medications,” Yacoubian said.

Compared with 62 age- and sex-matched people without the disease (controls), Parkinson’s patients showed significantly worse scores on measures of motor function and cognition. This was generally consistent with the symptoms of the disease.

Analyzing blood, fluids

To assess inflammatory status, the researchers first analyzed participants’ blood samples, as well as samples of the fluid around the brain and spinal cord from a subset of participants.

Results showed that Parkinson’s patients had significantly higher levels of certain inflammatory molecules and inflammatory T-cells relative to controls. Patients also had lower counts of regulatory T-cells (Tregs), a specific group of immune cells with anti-inflammatory activity.

“This decrease in Tregs and increase in non-Tregs suggests a deficient anti-inflammatory response, which may promote chronic inflammation” in Parkinson’s, the researchers wrote.

The scientists also assessed inflammation by using positron emission tomography (PET) imaging to detect TSPO, a protein produced by inflammatory brain immune cells called microglia, as well as by other types of inflammatory immune cells.

The scientists were the first in the U.S. to use 18F-DPA-714, a marker used to detect TSPO on PET imaging that was developed in Europe. The marker is injected into a person’s bloodstream, and it causes tissue that’s dense with TSPO protein to glow on the PET scan.

“Our multimodal study provides further evidence that TSPO signal as measured by 18F-DPA-714 is a marker of inflammation,” Yacoubian said.

Data showed increased TSPO levels in most brain regions among Parkinson’s patients relative to controls, such as in the thalamus, a region that helps relay signals through different parts of the brain.

“We found elevations in TSPO binding in untreated subjects at early stages of Parkinson’s, indicating the presence of inflammation. Our data clearly demonstrate that increased TSPO binding is present in Parkinson’s independent of treatment effects,” Yacoubian said.

Additional analyses in Parkinson’s patients showed that higher TSPO levels in the thalamus and other brain regions were associated significantly with scores on cognitive tests and with blood levels of some inflammatory molecules.

This is consistent with other research suggesting an association between damage to the thalamus and cognitive problems in Parkinson’s, the researchers noted.

“This study supports the conclusion that central inflammation is observed early in the disease process in [Parkinson’s], is independent of treatment for [Parkinson’s], and is correlated with cognitive features and peripheral markers of inflammation,” the scientists wrote.

Follow-up continues

The team is continuing to follow and analyze this early-disease group of patients.

“Follow-up of these study subjects will be critical to determine the significance of early inflammatory changes and to observe whether certain inflammatory changes predict clinical progression,” Yacoubian said.

“We will continue to collect biospecimens annually to determine whether the inflammatory measures change over time in Parkinson’s disease. Future studies will need to examine the potential causal relationship between inflammation and neurodegeneration,” Yacoubian added.