Peripheral Inflammation Is Associated with Dopaminergic Degeneration in Parkinson's Disease.

Abstract

Peripheral inflammatory immune responses are suggested to play a major role in dopaminergic degeneration in Parkinson's disease (PD). The neutrophil-to-lymphocyte ratio (NLR) is a well-established biomarker of systemic inflammation in PD. Degeneration of the nigrostriatal dopaminergic system can be assessed in vivo using [123 I]FP-CIT single photon emission computed tomography imaging of striatal dopamine transporter (DAT) density. To assess the relationship between the peripheral immune profile (NLR, lymphocytes, and neutrophils) and striatal DAT density in patients with PD. We assessed clinical features, the peripheral immune profile, and striatal [123 I]FP-CIT DAT binding levels of 211 patients with PD (primary-cohort). Covariate-controlled associations between the immune response and striatal DAT levels were assessed using linear regression analyses. For replication purposes, we also studied a separate cohort of 344 de novo patients with PD enrolled in the Parkinson's Progression Markers Initiative (PPMI-cohort). A higher NLR was significantly associated with lower 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). Intriguingly, a lower lymphocyte count was significantly associated 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 not consistently 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). Our findings across two independent cohorts suggest a relationship between systemic inflammation and dopaminergic degeneration in patients with PD. This relationship was mainly driven by the lymphocyte count. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.