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Increased peripheral inflammation in asymptomatic leucine-rich repeat kinase 2 mutation carriers.
Mov Disord 2016; 31(6):889-97MD

Abstract

BACKGROUND

We aimed to determine if peripheral or central inflammatory cytokines are altered in healthy subjects carrying a leucine-rich repeat kinase 2 (LRRK2) G2019S mutation, and thus genetically at risk of Parkinson's disease (PD). We also aimed to identify differences in inflammatory cytokines between LRRK2 G2019S-associated and idiopathic PD once the disease manifests.

METHODS

Participants were genetically screened and phenotyped, and biological samples were collected and stored by the Michael J. Fox Foundation LRRK2 Cohort Consortium. Serum samples and matching clinical data were obtained from 71 asymptomatic LRRK2 G2019S mutation carriers (CSF n = 25), 75 neurologically normal controls (CSF n = 22), 75 idiopathic PD patients (CSF n = 29), and 76 PD patients with a LRRK2 G2019S mutation (CSF n = 20). Inflammatory cytokines were measured using multiplex enzyme-linked immunosorbent assays.

RESULTS

Serum levels of interleukin 1 beta could discriminate asymptomatic LRRK2 G2019S mutation carriers from controls, with a high inflammatory subgroup of carriers identified. This subgroup was significantly higher in a number of PD-implicated pro-inflammatory cytokines. Once PD had manifest, LRRK2 G2019S patients were discriminated from idiopathic PD by higher serum platelet-derived growth factor, and higher CSF vascular endothelial growth factor and interleukin 8.

CONCLUSIONS

The results suggest that peripheral inflammation is higher in a percentage of subjects carrying the LRRK2 G2019S mutation. Replication and longitudinal follow-up is required to determine whether the increased peripheral cytokines can predict clinical PD. Importantly, these biological changes were observed prior to the clinical manifestations thought to herald PD. © 2016 International Parkinson and Movement Disorder Society.

Authors+Show Affiliations

School of Medical Sciences, University of NSW, Kensington, Australia. Neuroscience Research Australia, Randwick, Australia.Faculty of Medicine and Health Sciences, Macquarie University, Australia.School of Medical Sciences, University of NSW, Kensington, Australia. Neuroscience Research Australia, Randwick, Australia.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

26917005

Citation

Dzamko, Nicolas, et al. "Increased Peripheral Inflammation in Asymptomatic Leucine-rich Repeat Kinase 2 Mutation Carriers." Movement Disorders : Official Journal of the Movement Disorder Society, vol. 31, no. 6, 2016, pp. 889-97.
Dzamko N, Rowe DB, Halliday GM. Increased peripheral inflammation in asymptomatic leucine-rich repeat kinase 2 mutation carriers. Mov Disord. 2016;31(6):889-97.
Dzamko, N., Rowe, D. B., & Halliday, G. M. (2016). Increased peripheral inflammation in asymptomatic leucine-rich repeat kinase 2 mutation carriers. Movement Disorders : Official Journal of the Movement Disorder Society, 31(6), pp. 889-97. doi:10.1002/mds.26529.
Dzamko N, Rowe DB, Halliday GM. Increased Peripheral Inflammation in Asymptomatic Leucine-rich Repeat Kinase 2 Mutation Carriers. Mov Disord. 2016;31(6):889-97. PubMed PMID: 26917005.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Increased peripheral inflammation in asymptomatic leucine-rich repeat kinase 2 mutation carriers. AU - Dzamko,Nicolas, AU - Rowe,Dominic B, AU - Halliday,Glenda M, Y1 - 2016/02/25/ PY - 2015/09/18/received PY - 2015/11/13/revised PY - 2015/12/13/accepted PY - 2016/2/27/entrez PY - 2016/2/27/pubmed PY - 2017/12/28/medline KW - LRRK2 KW - Parkinson's KW - biomarker KW - cytokine KW - inflammation SP - 889 EP - 97 JF - Movement disorders : official journal of the Movement Disorder Society JO - Mov. Disord. VL - 31 IS - 6 N2 - BACKGROUND: We aimed to determine if peripheral or central inflammatory cytokines are altered in healthy subjects carrying a leucine-rich repeat kinase 2 (LRRK2) G2019S mutation, and thus genetically at risk of Parkinson's disease (PD). We also aimed to identify differences in inflammatory cytokines between LRRK2 G2019S-associated and idiopathic PD once the disease manifests. METHODS: Participants were genetically screened and phenotyped, and biological samples were collected and stored by the Michael J. Fox Foundation LRRK2 Cohort Consortium. Serum samples and matching clinical data were obtained from 71 asymptomatic LRRK2 G2019S mutation carriers (CSF n = 25), 75 neurologically normal controls (CSF n = 22), 75 idiopathic PD patients (CSF n = 29), and 76 PD patients with a LRRK2 G2019S mutation (CSF n = 20). Inflammatory cytokines were measured using multiplex enzyme-linked immunosorbent assays. RESULTS: Serum levels of interleukin 1 beta could discriminate asymptomatic LRRK2 G2019S mutation carriers from controls, with a high inflammatory subgroup of carriers identified. This subgroup was significantly higher in a number of PD-implicated pro-inflammatory cytokines. Once PD had manifest, LRRK2 G2019S patients were discriminated from idiopathic PD by higher serum platelet-derived growth factor, and higher CSF vascular endothelial growth factor and interleukin 8. CONCLUSIONS: The results suggest that peripheral inflammation is higher in a percentage of subjects carrying the LRRK2 G2019S mutation. Replication and longitudinal follow-up is required to determine whether the increased peripheral cytokines can predict clinical PD. Importantly, these biological changes were observed prior to the clinical manifestations thought to herald PD. © 2016 International Parkinson and Movement Disorder Society. SN - 1531-8257 UR - https://www.unboundmedicine.com/medline/citation/26917005/Increased_peripheral_inflammation_in_asymptomatic_leucine_rich_repeat_kinase_2_mutation_carriers_ L2 - https://doi.org/10.1002/mds.26529 DB - PRIME DP - Unbound Medicine ER -