Immune cell alterations in blood tied to Parkinson’s neurodegeneration

Greater neutrophil-to-lymphocyte ratio, fewer dopamine-producing nerve cells linked

Lindsey Shapiro, PhD avatar

by Lindsey Shapiro, PhD |

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A higher neutrophil-to-lymphocyte ratio and low lymphocyte counts in the bloodstream, thought to reflect greater systemic inflammation, were associated with fewer dopamine-producing nerve cells in the brains of Parkinson’s disease patients, a study showed.

These immune alterations were also generally linked to worse motor function across both groups.

The findings support a potential link between inflammation and neurodegeneration in Parkinson’s, the authors noted, but more research is needed to establish a “cause and effect relationship.”

“A better understanding of the role of the peripheral inflammatory immune responses in the complex [disease-causing] mechanisms in [Parkinson’s] is also likely to have therapeutic implications in the future,” the scientists wrote in “Peripheral Inflammation Is Associated with Dopaminergic Degeneration in Parkinson’s Disease,” which was published in Movement Disorders

A feature of Parkinson’s disease is the progressive loss of dopamine-producing, or dopaminergic, nerve cells in the brain, particularly those that release dopamine in a region called the striatum.

The processes underlying that neurodegeneration are complex, but it’s thought that activating immune cells in the brain contribute to an inflammatory state that in part drives brain cell loss. There’s evidence an increased inflammatory state in the rest of the body, or the periphery, might also contribute to disease progression.

The researchers previously found that the number of immune lymphocytes was significantly decreased in the blood of Parkinson’s patients relative to healthy people, whereas the immune neutrophil count tended to be higher. Consequently, the neutrophil-to-lymphocyte ratio (NLR) was significantly higher in patients’ blood. NLR is a known indicator of peripheral inflammation, but it isn’t established whether it has a direct relationship to Parkinson’s neurodegeneration, leading the researchers to examine whether NLR in the bloodstream correlated with dopaminergic neuron loss in the striatum among 211 Parkinson’s patients (mean age, 56) seen at their movement disorders clinic. Most were involved in their previous study.

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Inflammation elevated in brains of newly diagnosed patients

Link between NLR, neurodegeneration

Dopamine-releasing cells in the striatum were quantified by visualizing the dopamine transporter (DAT), a protein that resides on those cells and helps carry the signaling chemical into and out of them. The presence of DAT in a given brain area reflects how many dopamine-releasing cells are there.

A significant negative correlation was observed between NLR and DAT levels in evaluated subregions of the striatum, namely, the caudate and the putamen. That means the higher the NLR, the fewer dopamine-producing cells were observed.

Lower lymphocyte counts were significantly associated with lower DAT levels in both the caudate and putamen, whereas higher neutrophils were linked to lower DAT only in the caudate.

The scientists sought to validate their findings in a separate group of 344 Parkinson’s patients in the Parkinson’s Progression Markers Initiative (PPMI), a large international study collecting various types of data from patients and healthy people over time.

This group was more newly diagnosed than the first group and hadn’t yet been treated with dopamine-replacing therapies at the time their data was collected for this analysis.

Similar to the first group, a higher NLR and lower lymphocyte counts were associated with reduced DAT in the caudate and putamen, however, neutrophil counts didn’t correlate with DAT in either region.

The findings add to evidence that supports the idea that an imbalance in lymphocytes contributes to the onset and progression of Parkinson’s, according to the authors.

In contrast, “neutrophil alterations might not be [primarily] related to neurodegeneration,” the researchers wrote, noting they could play a secondary role in maintaining chronic inflammation instead.

Higher scores on the Hoehn-Yahr (HY) scale, reflecting more severe motor impairments, were associated with lower DAT levels in both groups, in line with previous research. Worse HY scores tended to be linked to higher NLR and lower lymphocyte counts, although these findings didn’t always reach statistical significance.

Similarly, worse scores on the Movement Disorders Society-Unified Parkinson’s Disease Rating Scale part III — another measure of motor symptoms — were linked to lower DAT levels and higher NLR in the PPMI group.

“Altogether, our results suggest an intricate relationship between peripheral inflammation (higher NLR), dopaminergic neurodegeneration (lower striatal DAT levels), and worse motor impairment, even in early stages of [Parkinson’s],” the researchers wrote, adding their results “should be considered exploratory and require further investigation.”