Objective: To assess CSF and plasmatic levels of cytokines as potential biomarkers of PD and PD mild cognitive impairment (PD-MCI).

Background: Neuroinflammation may play a role in the pathogenesis of PD. Cytokine levels are increased and microglia is activated in several cerebral areas of PD patients. In addition, cognitive impairment has been associated with inflammation, as IL-6, IL-1, and IL-1ß CSF levels are increased in PD-MCI patients.

Methods: 40 PD patients and 40 controls underwent clinical and neuropsychological evaluation (at least two test for each cognitive domain) and lumbar puncture. According to their cognitive state patients were classified as cognitively normal (PDCN) (n=15) or with PD-MCI (n=22). CSF levels of IL-1ß, IL-2, IL-6, IFNγ, and TNF-α were measured using multiplex technology. Cytokines with detectable levels in CSF (IL-6 and TNF-α) were individually assessed in plasma using commercial ELISA kits (R&D Systems, Minneapolis, MN, USA).

Results: Concentration of IL-1ß, IL-2, and IFNγ in CSF were below the detection threshold in all the subjects. Levels of IL-6 did not differ between patients and controls (0.617 ± 0.30 vs. 0.531 ± 0.22 pg/mL; p=0.346). Adjusting for age, TNF-α levels were higher in patients than in controls (0.4013 ± 0.158 vs. 0.3078 ± 0.124 pg/mL; p=0.021. In plasma, IL-6 levels were not different between groups (2.294 ± 2.66 vs. 1.917 ± 1.27 pg/mL; p=0.742) and TNF-α levels were under the detection threshold. There was no difference in CSF IL-6 and TNF-α levels and plasmatic IL-6 levels between PDCN and PD-MCI patients. In contrast, IL-6 plasmatic levels negatively correlated with the composite z score of attention and working memory (r=-0.378; p=0.009), executive function (r=-0.359; p=0.016), language (r=-0.553; p<0.001), global cognition z score (r=-0.411; p=0.005), MMSE (r=-0.383; p=0.01), and MOCA (r=-0.429; p=0.003). After adjusting for age, only correlation with language remained significant (corrected p=0.009).

Conclusions: In PD patients, CSF levels of TNF-α are elevated and plasmatic levels of IL-6 negatively correlated with cognitive outcome in language. As decline in semantic fluency has been associated with progression to dementia, plasma IL-6 could deserve further studies as potential biomarker of cognitive dysfunction in PD.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/cytokines-in-csf-and-plasma-as-potential-biomarkers-for-pd-cognitive-impairment/