DIAGNOSTIC VALUE OF INFLAMMATORY PROCESSES IN DIFFERENTIATING PARKINSONISM SUBTYPES
Keywords:
Parkinson's disease, parkinsonism, gut-brain axis, interleukin-6, fecal calprotectin, Helicobacter pylori, neuroinflammationAbstract
The role of neuroinflammatory processes and the gut-brain axis in the pathogenesis of Parkinson's disease and other forms of parkinsonism has emerged as a priority research area in contemporary neurology. This study aimed to comprehensively evaluate systemic and intestinal inflammation in patients with Parkinson's disease and vascular parkinsonism through assessment of interleukin-6 (IL-6), fecal calprotectin levels, and Helicobacter pylori infection status, while analyzing their associations with clinical manifestations and disease progression. The findings demonstrated significantly elevated IL-6 and fecal calprotectin levels in Parkinson's disease patients compared to those with vascular parkinsonism, indicating more pronounced systemic and intestinal inflammatory responses. Statistically significant correlations were established between inflammatory biomarkers, severity of motor dysfunction, and clinical disease stage. The higher prevalence of Helicobacter pylori infection in Parkinson's disease patients and its correlation with clinical parameters confirm the pathogenetic significance of infectious factors in triggering the inflammatory cascade. These results provide evidence for the critical pathogenetic role of the gut-brain axis in Parkinson's disease development and reveal promising applications of inflammatory markers in differential diagnosis, risk stratification, and development of personalized therapeutic strategies.
References
Barichella M., Pacchetti C., Bolliri C. et al. Probiotics and prebiotic fiber for constipation associated with Parkinson disease: An RCT // Neurology. — 2019. — Vol. 92, №15. — P. e1764–e1771. — doi:10.1212/WNL.0000000000007240.
Braak H., Del Tredici K., Rüb U., de Vos R.A.I. et al. Staging of brain pathology related to sporadic Parkinson’s disease // Neurobiology of Aging. — 2003. — Vol. 24, №2. — P. 197–211. — doi:10.1016/S0197-4580(02)00065-9.
Devos D., Lebouvier T., Lardeux B. et al. Colonic inflammation in Parkinson’s disease // Neurobiology of Disease. — 2013. — Vol. 50. — P. 42–48. — doi:10.1016/j.nbd.2012.09.002.
Fasano A., Visanji N.P., Liu L.W.C., Lang A.E., Pfeiffer R.F. Gastrointestinal dysfunction in Parkinson’s disease // The Lancet Neurology. — 2015. — Vol. 14, №6. — P. 625–639. — doi:10.1016/S1474-4422(15)00007-1.
Fasano A., Visanji N.P., et al. Gut–brain axis and disease: focus on Parkinson’s disease // Movement Disorders. — 2015. — Vol. 30, №9. — P. 1187–1195.
Hasegawa S., et al. Intestinal dysbiosis and reduced clostridia in patients with Parkinson’s disease // PLoS ONE. — 2015. — Vol. 10, №11. — e0142164.
Holmay M.J., Terpstra M., Coles L.D. et al. N-acetylcysteine boosts brain and blood glutathione in Gaucher and Parkinson’s diseases // Clinical Neuropharmacology. — 2013. — Vol. 36, №4. — P. 103–106. — doi:10.1097/WNF.0b013e31829ae713.
Houser M.C., Tansey M.G. The gut-brain axis: is intestinal inflammation a silent driver of Parkinson’s disease pathogenesis? // NPJ Parkinson’s Disease. — 2017. — Vol. 3. — P. 3. — doi:10.1038/s41531-016-0002-0.
Mischley L.K., Standish L.J., Weiss S., Padowski J.M. Nutrition and Parkinson’s disease: emerging evidence for a role of the gut microbiome // Frontiers in Neurology. — 2017. — Vol. 8. — P. 161. — doi:10.3389/fneur.2017.00161.
Monti D.A., Zabrecky G., Kremens D. et al. N-acetyl cysteine is associated with dopaminergic improvement in Parkinson’s disease // Clinical Pharmacology & Therapeutics. — 2016. — Vol. 99, №5. — P. 648–655. — doi:10.1002/cpt.329.
Mulak A., Bonaz B. Brain-gut-microbiota axis in Parkinson’s disease // World Journal of Gastroenterology. — 2015. — Vol. 21, №37. — P. 10609–10620. — doi:10.3748/wjg.v21.i37.10609.
Qin L., Liu Y., Wang T., Wei S.J. et al. NADPH oxidase mediates lipopolysaccharide-induced neurotoxicity and proinflammatory gene expression in activated microglia // The Journal of Biological Chemistry. — 2004. — Vol. 279, №2. — P. 1415–1421. — doi:10.1074/jbc.M307657200.
Reale M., et al. Cytokine pattern in peripheral blood mononuclear cells of Parkinson’s disease patients // Neuropsychobiology. — 2009. — Vol. 59, №2. — P. 103–107.
Samson K., Garcia-Pagan C., Mosquera-Romero E. et al. The gut microbiota and Parkinson’s disease: physiological regulation and therapeutic potential // Frontiers in Neurology. — 2021. — Vol. 12. — P. 667709. — doi:10.3389/fneur.2021.667709.
Scheperjans F., Aho V., Pereira P.A. et al. Gut microbiota are related to Parkinson’s disease and clinical phenotype // Movement Disorders. — 2015. — Vol. 30, №3. — P. 350–358. — doi:10.1002/mds.26069.
Schwiertz A., Spiegel J., Dillmann U. et al. Fecal markers of intestinal inflammation and intestinal permeability are elevated in Parkinson’s disease // Neurogastroenterology & Motility. — 2018. — Vol. 30, №9. — e13479. — doi:10.1111/nmo.13479.
Tansey M.G., Wallings R.L., Houser M.C. et al. Inflammation and immune dysfunction in Parkinson disease // Nature Reviews Immunology. — 2022. — Vol. 22, №8. — P. 485–498. — doi:10.1038/s41577-022-00699-1.
Tamtaji O.R., Taghizadeh M., Daneshvar K. et al. Clinical and metabolic response to probiotic administration in people with Parkinson’s disease: a randomized, double-blind, placebo-controlled trial // Clinical Nutrition. — 2019. — Vol. 38, №3. — P. 1031–1035. — doi:10.1016/j.clnu.2018.05.018.
Wells P.S., Freedman M.S., Mayo N.E. et al. The role of genetic polymorphisms in detoxification enzymes and susceptibility to neurodegenerative disorders // Journal of Neurology, Neurosurgery & Psychiatry. — 2000. — Vol. 68, №2. — P. 237–240. — doi:10.1136/jnnp.68.2.237.
Zhu M. et al. Gut Microbiota: A Novel Therapeutic Target for Parkinson’s // Frontiers in Immunology. — 2022.