Peripheral inflammation is associated with dopaminergic degeneration in Parkinson's disease
Peripheral inflammation is associated with dopaminergic degeneration in Parkinson's disease
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Original abstract
Background: Peripheral inflammatoryimmune responses are suggested to play a major role indopaminergic degeneration in Parkinson’s disease (PD).The neutrophil-to-lymphocyte ratio (NLR) is a well-established biomarker of systemic inflammation inPD. Degeneration of the nigrostriatal dopaminergic sys-tem can be assessed in vivo using [123 I]FP-CIT singlephoton emission computed tomography imaging ofstriatal dopamine transporter (DAT) density.Objectives: To assess the relationship between theperipheral immune profile (NLR, lymphocytes, and neu-trophils) and striatal DAT density in patients with PD.Methods: We assessed clinical features, the peripheralimmune profile, and striatal [ 123 I]FP-CIT DAT bindinglevels of 211 patients with PD (primary-cohort).Covariate-controlled associations between the immuneresponse and striatal DAT levels were assessed usinglinear regression analyses. For replication purposes, wealso studied a separate cohort of 344 de novo patientswith PD enrolled in the Parkinson’s Progression MarkersInitiative (PPMI-cohort).Results: A higher NLR was significantly associated withlower DAT levels in the caudate (primary-cohort:β = 0.01, p < 0.001; PPMI-cohort: β = 0.05,p = 0.05) and the putamen (primary-cohort: β = 0.05,p = 0.02; PPMI-cohort: β = 0.06, p = 0.02). Intrigu-ingly, a lower lymphocyte count was significantlyassociated with lower DAT levels in both the caudate(primary-cohort: β = +0.09, p < 0.05; PPMI-cohort:β = +0.11, p = 0.02) and the putamen (primary-cohort:β = +0.09, p < 0.05, PPMI-cohort: β = +0.14, p = 0.01),but an association with the neutrophil count was notconsistently observed (caudate; primary-cohort:β = 0.05, p = 0.02; PPMI-cohort: β = 0, p = 0.94; putamen; primary-cohort: β = 0.04, p = 0.08; PPMI cohort: β = 0.01, p = 0.73). Conclusions: Our findings across two independent cohorts suggest a relationship between systemic inflam mation and dopaminergic degeneration in patients with PD. This relationship was mainly driven by the lympho cyte count. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of Interna tional Parkinson and Movement Disorder Society.