Objective: To investigate the association between plasma fibrinogen (Fib) levels, clinical features, and nigrostriatal dopaminergic neurodegeneration in drug-naïve patients with Parkinson’s disease (PD).

Background: Fib is elevated under inflammatory conditions. Emerging experimental evidence suggests that fibrinogen promotes aggregation of pathological α-synuclein and amyloid-β deposition, implicating it in neurodegenerative processes.

Method: We enrolled 144 newly diagnosed, untreated patients with PD. Clinical assessments included age, sex, disease duration, the Unified Parkinson’s Disease Rating Scale part III (UPDRS III), the Mini-Mental State Examination (MMSE), and olfactory function. Nigrostriatal dopaminergic integrity was assessed using dopamine transporter imaging (DaT scan), and the mean specific binding ratio (SBR) of the bilateral striata was calculated. To examine whether Fib reflects systemic inflammation, correlations were evaluated with established peripheral inflammatory indices, including the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and systemic immune-inflammation index (SII).

Results: The cohort had a mean age of 69 ± 10 years; 77 patients (53%) were male, and the mean disease duration was 1.9 ± 1.6 years. The mean Fib level was 307 ± 62 mg/dL. Fib levels tended to be higher in women than in men (299 ± 51 vs. 284 ± 60 mg/dL, p = 0.061) and showed a weak but significant positive correlation with UPDRS III scores (r = 0.167, p = 0.024). Fib was positively correlated with age (r = 0.301, p < 0.001) and inversely correlated with MMSE (r = −0.266, p < 0.001) and SBR (r = −0.290, p < 0.001). In multivariable regression analyses adjusting for age, sex, and UPDRS III, Fib remained independently associated with MMSE (β = −0.240, p = 0.006) and SBR (β = −0.211, p = 0.027). In contrast, Fib showed no significant associations with NLR, PLR, or SII.

Conclusion: Elevated Fib levels were associated with cognitive impairment and nigrostriatal dopaminergic degeneration in PD, consistent with a potential role for Fib as a biomarker of neurodegenerative pathology. Importantly, Fib was not correlated with conventional peripheral inflammatory markers, supporting the notion that it may promote neurodegeneration through pathways distinct from systemic inflammation.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/plasma-fibrinogen-associates-with-dopaminergic-neurodegeneration-independent-of-peripheral-inflammation-in-drug-naive-parkinsons-disease/