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. 2023 May;38(5):755-763.
doi: 10.1002/mds.29369. Epub 2023 Mar 13.

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

Laura Muñoz-Delgado  1   2 , Miguel Ángel Labrador-Espinosa  1   2   3 , Daniel Macías-García  1   2 , Silvia Jesús  1   2 , Belén Benítez Zamora  1 , Paula Fernández-Rodríguez  1   4 , Astrid D Adarmes-Gómez  1   2 , María Isabel Reina Castillo  1 , Sandra Castro-Labrador  1 , Jesús Silva-Rodríguez  1 , Fátima Carrillo  1   2 , David García Solís  4 , Michel J Grothe  1   2 , Pablo Mir  1   2   3
Affiliations

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

Laura Muñoz-Delgado et al. Mov Disord. 2023 May.

Abstract

Background: 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.

Objectives: To assess the relationship between the peripheral immune profile (NLR, lymphocytes, and neutrophils) and striatal DAT density in patients with PD.

Methods: 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).

Results: 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).

Conclusions: 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.

Keywords: Parkinson's disease; [123I]FP-CIT SPECT; inflammation; neurodegeneration; neutrophil-to-lymphocyte ratio.

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References

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