Study Finds Inflammatory, Senescence Markers May Predict Progression of Parkinson Disease

Scientists still have a long way to go to fully understand the complex pathology of Parkinson disease (PD), but a new study lends credence to the idea that inflammatory and senescence markers could be meaningful data points to help clinicians predict the progression of the disease.

A team of investigators from British and Irish universities wanted to find out whether markers of senescence, such as telomere length and the cyclin-dependent kinase inhibitors p16 and p21, might be predictive of cognitive and motor progression among newly diagnosed patients with Parkinson.

To find out, they launched the ICICLE-PD study, following a group of newly diagnosed patients and assessing physical and cognitive markers for 36 months. The findings were published in the Journal of Parkinson’s Disease.

“Our particular study used blood-derived samples from the baseline and 18 months and we found that, at least in our cohort of 154 PD patients and 99 controls from the Newcastle and Gateshead region, that PD patients had a shorter telomere length in their blood monocytes together with a faster telomere shortening during the first 18 months,” said corresponding author Gabriele Saretzki, PhD, of Newcastle University.

The team also looked at whether their chosen biomarkers of cell senescence and/or inflammatory markers could predict the likelihood of a patient with PD developing cognitive impairment up to dementia.

“For the cognitive decline we found that 5 selected inflammatory markers which had been analyzed at baseline and published previously were the best predictors,” Saretzki said. “For the few dementia cases after 36 months of following those PD patients, we found that these patients had much shorter telomere length in their blood cells than those other patients that had not yet developed dementia and might never do [so].”

Saretzki said a number of patients who had not yet developed dementia at the time of the study’s end have subsequently progressed to dementia, but she said the investigators have yet to analyze those patients.

Saretzki cautioned that other studies have found different results, and so she said it’s important not to over-interpret the findings of this particular study. She also noted that her team’s biomarker analysis is a cross-sectional study, thus it merely represents the tendencies within a particular cohort and is not yet suitable for application as a diagnostic tool on the individual-patient level. In addition, she said, telomere length can be affected by a number of different factors aside from Parkinson’s, including genetic make-up, the environment, and oxidative stress. However, she said it’s possible that increased inflammation in blood serum can lead to oxidative stress that in turn accelerates telomere shortening.

“All of these parameters, which we have analyzed in blood, can also be part of a systemic response which likewise influences biological and clinical properties in the brain, the main organ of PD,” she said. “Thus, further research on model systems and a better understanding of the underlying molecular mechanisms are required before our findings might translate into some useful diagnostic and, based on that, into therapeutic strategies to combat and modify the disease.”

Reference

Martin-Ruiz C, Williams-Gray CH, Yarnall AJ, et al. Senescence and inflammatory markers for predicting clinical progression in parkinson’s disease: The ICICLE-PD study. J Parkinsons Dis. 2020;10(1):193-206. doi:10.3233/jpd-191724.