Mutations in GBA and LRRK2 Are Not Associated with Increased Inflammatory Markers.

Autor: Thaler A; Movement Disorders Unit, Neurological Institute, Tel-Aviv Medical Center, Tel-Aviv, Israel.; Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel.; Sagol School of Neuroscience, Tel-Aviv University, Tel-Aviv, Israel.; Laboratory of Early Markers of Neurodegeneration, Neurological Institute, Tel-Aviv Medical Center, Tel-Aviv, Israel., Omer N; Movement Disorders Unit, Neurological Institute, Tel-Aviv Medical Center, Tel-Aviv, Israel.; Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel.; Laboratory of Early Markers of Neurodegeneration, Neurological Institute, Tel-Aviv Medical Center, Tel-Aviv, Israel., Giladi N; Movement Disorders Unit, Neurological Institute, Tel-Aviv Medical Center, Tel-Aviv, Israel.; Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel.; Sagol School of Neuroscience, Tel-Aviv University, Tel-Aviv, Israel., Gurevich T; Movement Disorders Unit, Neurological Institute, Tel-Aviv Medical Center, Tel-Aviv, Israel.; Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel.; Sagol School of Neuroscience, Tel-Aviv University, Tel-Aviv, Israel., Bar-Shira A; Genetic Institute, Tel-Aviv Medical Center, Tel-Aviv, Israel., Gana-Weisz M; Genomic Research Laboratory for Neurodegeneration, Tel-Aviv Medical Center, Tel-Aviv, Israel., Goldstein O; Genomic Research Laboratory for Neurodegeneration, Tel-Aviv Medical Center, Tel-Aviv, Israel., Kestenbaum M; Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel.; Neurology Department, Meir Hospital, Kfar-Saba, Israel., Shirvan JC; Biogen Inc, Cambridge, MA, USA., Cedarbaum JM; Biogen Inc, Cambridge, MA, USA.; Coeruleus Clinical Sciences LLC, Woodbridge, CT, USA., Orr-Urtreger A; Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel.; Sagol School of Neuroscience, Tel-Aviv University, Tel-Aviv, Israel.; Genomic Research Laboratory for Neurodegeneration, Tel-Aviv Medical Center, Tel-Aviv, Israel., Regev K; Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel.; Neuroimmunology Unit, Neurological Institute, Tel-Aviv Medical Center, Tel-Aviv, Israel., Shenhar-Tsarfaty S; Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel.; Department of Internal Medicine 'C', 'D', and 'E', Tel-Aviv Medical Center, Tel-Aviv, Israel., Mirelman A; Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel.; Sagol School of Neuroscience, Tel-Aviv University, Tel-Aviv, Israel.; Laboratory of Early Markers of Neurodegeneration, Neurological Institute, Tel-Aviv Medical Center, Tel-Aviv, Israel.
Jazyk: angličtina
Zdroj: Journal of Parkinson's disease [J Parkinsons Dis] 2021; Vol. 11 (3), pp. 1285-1296.
DOI: 10.3233/JPD-212624
Abstrakt: Background: Inflammation is an integral part of neurodegeneration including in Parkinson's disease (PD). Ashkenazi Jews have high rates of genetic PD with divergent phenotypes among GBA-PD and LRRK2-PD. The role of inflammation in the prodromal phase of PD and the association with disease phenotype has yet to be elucidated.
Objective: To assess central and peripheral cytokines among PD patients with mutations in the LRRK2 and GBA genes and among non-manifesting carriers (NMC) of these mutations in order to determine the role of inflammation in genetic PD.
Methods: The following cytokines were assessed from peripheral blood and cerebrospinal fluid (CSF): TNF-α, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10 and INF- γ. A comprehensive intake including general medical conditions, use of anti-inflammatory treatments, motor and cognitive assessments and additional laboratory measures were recorded, enabling the construction of the MDS probable prodromal score.
Results: Data from 362 participants was collected: 31 idiopathic PD (iPD), 30 LRRK2-PD, 77 GBA-PD, 3 homozygote GBA-PD, 3 GBA-LRRK2-PD, 67 LRRK2-NMC, 105 GBA-NMC, 14 LRRK2-GBA-NMC, and 32 healthy controls. No between-group differences in peripheral or CSF cytokines were detected. No correlation between disease characteristics or risk for prodromal PD could be associated with any inflammatory measure.
Conclusion: In this study, we could not detect any evidence on dysregulated immune response among GBA and LRRK2 PD patients and non-manifesting mutation carriers.
Databáze: MEDLINE
Externí odkaz: