Objective: To discriminate affected PARK-Parkin and PARK-PINK1 mutation carriers from idiopathic Parkinson’s disease (PD) patients and healthy controls using serum IL-6 and mtDNA levels.

Background: Serum samples from PD patients contain elevated levels of proinflammatory cytokines. However, whether inflammation is the consequence of neurodegeneration or contributes to the disease itself remains unknown. Recently, studies in murine models suggest that an impaired degradation of dysfunctional mitochondria leads to increased IL-6 levels via a STING-dependent mechanism triggered by damage-associated molecular patterns (DAMPs) including mtDNA. Findings from a small published cohort corroborated increased IL6 levels in serum samples from human Parkin biallelic mutation carriers compared to healthy controls. In order to independently replicate these results, we analyzed serum levels of IL-6 and mtDNA in a large cohort of monogenic and idiopathic PD patients (IPD), and healthy controls (HC).

Method: We analyzed IL-6 serum levels from 23 Parkin biallelic, 36 Parkin heterozygous, 11 PINK1 biallelic, 20 PINK1 heterozygous, 15 GBA, and 10 LRRK2 mutation carriers as well as from 73 IPD patients, and 125 HC in a certified diagnostic laboratory. Samples originated from three independent centers. Additionally, we assessed mtDNA levels in a subset of the cohort.

Results: Our data from two German centers revealed increased IL-6 levels in Parkin/PINK1 biallelic mutation carriers (n = 15; 7.1 +/- 1.8 pg/ml) compared to HC (n = 110; 5.5 +/- 1.6 pg/ml). This difference was absent in LRRK2 and GBA mutation carriers. The investigation of a third independent cohort from Italy confirmed elevated IL-6 levels in patients with Parkin/PINK1-associated PD. Furthermore, we observed increased mtDNA levels in biallelic and affected heterozygous Parkin/PINK1 patients (n = 30; 1.1 +/- 1.1) compared to HC (n = 103; 0.41 +/- 0.38).

Conclusion: Our findings support the link between Parkin/PINK1-associated PD and inflammation. Increased mtDNA levels were consistent with increased IL-6 levels supporting the role of DAMPs also in human PD caused by mutations in Parkin/PINK1. Our findings have potential translational impact since alterations in cytokine and mtDNA levels may serve as biomarkers or therapeutic targets.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/evaluating-il6-and-mitochondrial-dna-levels-as-a-potential-biomarker-in-carriers-of-parkin-and-pink1-mutations/