Neutrophil-to-lymphocyte ratio and lymphocyte count reflect alterations in central neurodegeneration-associated proteins and clinical severity in Parkinson Disease patients

Grillo, Piergiorgio; Sancesario, Giulia Maria; Bovenzi, Roberta; Zenuni, Henri; Bissacco, Jacopo; Mascioli, Davide; Simonetta, Clara; Forti, Paolo; Degoli, Giulia Rebecca; Pieri, Massimo; Chiurchiù, Valerio; Stefani, Alessandro; Mercuri, Nicola Biagio; Schirinzi, Tommaso

doi:10.1016/j.parkreldis.2023.105480

Cited by 9 publications

(1 citation statement)

References 11 publications

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“…Clinical research have consistently found a decrease in lymphocyte count in PD patients, which is also the reason for the increase in NLR ( Tansey and Romero-Ramos, 2019 ; Pajares, 2020 ; Grillo et al, 2023 ). Moreover, a recent study reported that a lower lymphocyte count was associated with an increased risk of subsequent PD ( Jensen et al, 2021 ).…”

Section: Discussionmentioning

confidence: 97%

Association analysis of dopaminergic degeneration and the neutrophil-to-lymphocyte ratio in Parkinson’s disease

Zhang,

Chen,

Ren

et al. 2024

Front. Aging Neurosci.

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IntroductionPeripheral inflammatory responses are suggested to play a major role in the pathophysiology of Parkinson’s disease (PD). The neutrophil-to-lymphocyte ratio (NLR), a new recognized biomarker, can reflect peripheral inflammation in PD. However, the association between the NLR and dopaminergic degeneration in PD remains unclear.MethodsIn this retrospective study, 101 enrolled PD patients were categorized into early-stage and advanced-stage PD based on the Hoehn and Yahr (HY) scale. We evaluated the clinical characteristics, peripheral immune profile, and 11C-CFT striatal dopamine transporter (DAT) binding levels. Linear regression analyses were employed to assess the associations between NLR and striatal DAT levels at different stages in PD patients.ResultsCovariate-controlled regression analysis revealed that higher NLR was significantly associated with lower DAT levels in the caudate (β = −0.27, p = 0.003) and the putamen (β = −0.27, p = 0.011). Moreover, in the early-stage PD subgroup, a similar association was observed (caudate: β = −0.37, p = 0.013; putamen: β = −0.45, p = 0.005). The lymphocytes count was correlated positively with the striatal DAT levels in the Spearman correlation analysis whether in total patients (caudate: ρ = 0.25, p = 0.013; putamen: ρ = 0.22, p = 0.026) or in the early-stage subgroup (caudate: ρ = 0.31, p = 0.023, putamen: ρ = 0.34, p = 0.011).ConclusionDopaminergic degeneration is associated with peripheral inflammation in PD. The NLR, a widely used inflammatory marker, may have the potential to reflect the degree of dopaminergic degeneration in individuals with early-stage PD.

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Section: Discussionmentioning

confidence: 97%

Association analysis of dopaminergic degeneration and the neutrophil-to-lymphocyte ratio in Parkinson’s disease

Zhang,

Chen,

Ren

et al. 2024

Front. Aging Neurosci.

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Neutrophil‐to‐lymphocyte ratio and longitudinal cognitive performance in Parkinson's disease

Lucero,

Gurnani,

Weinberg

et al. 2024

Ann Clin Transl Neurol

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ObjectivePrevious studies have suggested a link between peripheral inflammation and cognitive outcomes in the general population and individuals with Parkinson's disease (PD). We sought to test the association between peripheral inflammation, measured by the neutrophil‐to‐lymphocyte ratio (NLR), cognitive performance, and mild cognitive impairment (MCI) status in individuals with PD.MethodsA retrospective, longitudinal analysis was carried out using data from the Parkinson's Progression Markers Initiative (PPMI), including 422 participants with PD followed over 5 years. Cognitive performance was assessed using a neuropsychological battery including the Montreal Cognitive Assessment (MoCA) and tests of verbal learning, visuospatial function, processing speed, and executive function. Mixed‐effect regression models were used to analyze the association between NLR, cognitive performance, and MCI status, controlling for age, sex, education, APOE genotype, and motor severity.ResultsThere was a negative association between NLR and MoCA, even after adjusting for covariates (b = −0.12, p = 0.033). MoCA scores for individuals in the high NLR category exhibited a more rapid decline over time compared to the low NLR group (b = −0.16, p = 0.012). Increased NLR was associated with decreased performance across all cognitive domains. However, NLR was not associated with MCI status over 5 years of follow‐up.InterpretationThis study demonstrates a link between elevated NLR and cognitive performance in PD, but not with MCI status over 5 years. This suggests that NLR is more strongly associated with day‐to‐day cognitive performance than with incident MCI, but this requires further study in more heterogeneous cohorts.

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Immunometabolic Signature and Tauopathy Markers in Blood Cells of Progressive Supranuclear Palsy

Rosina,

Veltri,

Nesci

et al. 2024

Movement Disorders

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BackgroundPeripheral immune cells critically contribute to the clinical‐pathological progression of neurodegenerative diseases and also represent a reliable frame for translational applications. However, data on progressive supranuclear palsy (PSP) are almost scarce in this regard.ObjectiveOur goal is to provide a broad biological characterization of peripheral immune cells in a selected PSP cohort.MethodsSeventy‐one PSP patients scored on the PSP Rating Scale (PSPRS), and 59 controls were enrolled. The blood cell count was collected, together with the neutrophil‐to‐lymphocyte ratio (NLR) calculation. In a subgroup of patients and controls, the peripheral blood mononuclear cells (PBMCs) were analyzed by the mitochondrial bioenergetic performance and the western blot assay of the nuclear factor erythroid 2‐related factor (NRF2)/heme oxygenase 1 (HO‐1) pathway and the total tau (t‐tau) and phosphorylated tau (p‐tau) proteins. Case–control comparison and correlation analyses were performed.ResultsPSP patients had a NLR higher than controls, with increased circulating neutrophils. The leukocyte metabolism was also globally increased and the NRF2/HO‐1 pathway activated in patients. P‐tau, but not t‐tau, significantly accumulated in PSP PBMCs and inversely correlated with the PSPRS.ConclusionsPSP displays a systemic inflammatory shift of the peripheral immunity, which may justify a metabolic reprogramming of the blood leukocytes. Consistently, the NRF2/HO‐1 pathway, a master regulator of inflammatory and metabolic response, was activated. PBMCs also engulf tau proteins, especially p‐tau, in a way inverse to the disease severity, allowing for a peripheral tracking of tauopathy in patients. Immunometabolic targets may, therefore, gain relevance to PSP in biomarker or therapeutic purposes. © 2024 International Parkinson and Movement Disorder Society.

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Neutrophil-to-lymphocyte ratio and lymphocyte count reflect alterations in central neurodegeneration-associated proteins and clinical severity in Parkinson Disease patients

Cited by 9 publications

References 11 publications

Association analysis of dopaminergic degeneration and the neutrophil-to-lymphocyte ratio in Parkinson’s disease

Association analysis of dopaminergic degeneration and the neutrophil-to-lymphocyte ratio in Parkinson’s disease

Neutrophil‐to‐lymphocyte ratio and longitudinal cognitive performance in Parkinson's disease

Immunometabolic Signature and Tauopathy Markers in Blood Cells of Progressive Supranuclear Palsy

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