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Candidate inflammatory biomarkers display unique relationships with alpha-synuclein and correlate with measures of disease severity in subjects with Parkinson's disease.
J Neuroinflammation. 2017 Aug 18; 14(1):164.JN

Abstract

BACKGROUND

Efforts to identify fluid biomarkers of Parkinson's disease (PD) have intensified in the last decade. As the role of inflammation in PD pathophysiology becomes increasingly recognized, investigators aim to define inflammatory signatures to help elucidate underlying mechanisms of disease pathogenesis and aid in identification of patients with inflammatory endophenotypes that could benefit from immunomodulatory interventions. However, discordant results in the literature and a lack of information regarding the stability of inflammatory factors over a 24-h period have hampered progress.

METHODS

Here, we measured inflammatory proteins in serum and CSF of a small cohort of PD (n = 12) and age-matched healthy control (HC) subjects (n = 6) at 11 time points across 24 h to (1) identify potential diurnal variation, (2) reveal differences in PD vs HC, and (3) to correlate with CSF levels of amyloid β (Aβ) and α-synuclein in an effort to generate data-driven hypotheses regarding candidate biomarkers of PD.

RESULTS

Despite significant variability in other factors, a repeated measures two-way analysis of variance by time and disease state for each analyte revealed that serum IFNγ, TNF, and neutrophil gelatinase-associated lipocalin (NGAL) were stable across 24 h and different between HC and PD. Regression analysis revealed that C-reactive protein (CRP) was the only factor with a strong linear relationship between CSF and serum. PD and HC subjects showed significantly different relationships between CSF Aβ proteins and α-synuclein and specific inflammatory factors, and CSF IFNγ and serum IL-8 positively correlated with clinical measures of PD. Finally, linear discriminant analysis revealed that serum TNF and CSF α-synuclein discriminated between PD and HC with a minimum of 82% sensitivity and 83% specificity.

CONCLUSIONS

Our findings identify a panel of inflammatory factors in serum and CSF that can be reliably measured, distinguish between PD and HC, and monitor inflammation as disease progresses or in response to interventional therapies. This panel may aid in generating hypotheses and feasible experimental designs towards identifying biomarkers of neurodegenerative disease by focusing on analytes that remain stable regardless of time of sample collection.

Authors+Show Affiliations

Department of Physiology, Emory University, 615 Michael Street, 605L Whitehead Biomedical Res. Bldg., Atlanta, GA, 30322, USA.Department of Physiology, Emory University, 615 Michael Street, 605L Whitehead Biomedical Res. Bldg., Atlanta, GA, 30322, USA.Department of Physiology, Emory University, 615 Michael Street, 605L Whitehead Biomedical Res. Bldg., Atlanta, GA, 30322, USA.Department of Physiology, Emory University, 615 Michael Street, 605L Whitehead Biomedical Res. Bldg., Atlanta, GA, 30322, USA.Department of Physiology, Emory University, 615 Michael Street, 605L Whitehead Biomedical Res. Bldg., Atlanta, GA, 30322, USA.Department of Biostatistics, University of Iowa, 145 N. Riverside Drive, 100 CPHB, Iowa City, Iowa, 52242, USA.BioLegend, Inc., 180 Rustcraft Rd # 140, Dedham, Massachusetts, 02026, USA.Paracelsus-Elena-Klinik, 34128 Kassel, Kassel, Germany. Georg-August University Medical Center Goettingen, 37075, Goettingen, Germany.Program in Neuroscience and Division of Neurology, The Ottawa Hospital, University of Ottawa Brain & Mind Institute, 451 Smyth Road, Room 1412, Ottawa, K1H 8M5, Canada.Follow the Molecule, 143 Voyage Mall, Marina del Rey, CA, 90292, USA.PAREXEL International, Early Phase Unit, 1560 E. Chevy Chase Drive, Suite 140, Glendale, CA, 91206, USA.Research Programs, The Michael J. Fox Foundation for Parkinson's Research, 69 7th Avenue, 498, New York, NY, 10018, USA.Research Programs, The Michael J. Fox Foundation for Parkinson's Research, 69 7th Avenue, 498, New York, NY, 10018, USA.Yale-New Haven Hospital, 20 York Street, New Haven, CT, 06510, USA.Nell Hodgson Woodruff School of Nursing, Emory University, 1520 Clifton Rd, Atlanta, GA, 30322, USA.Department of Physiology, Emory University, 615 Michael Street, 605L Whitehead Biomedical Res. Bldg., Atlanta, GA, 30322, USA. malu.tansey@emory.edu.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

28821274

Citation

Eidson, Lori N., et al. "Candidate Inflammatory Biomarkers Display Unique Relationships With Alpha-synuclein and Correlate With Measures of Disease Severity in Subjects With Parkinson's Disease." Journal of Neuroinflammation, vol. 14, no. 1, 2017, p. 164.
Eidson LN, Kannarkat GT, Barnum CJ, et al. Candidate inflammatory biomarkers display unique relationships with alpha-synuclein and correlate with measures of disease severity in subjects with Parkinson's disease. J Neuroinflammation. 2017;14(1):164.
Eidson, L. N., Kannarkat, G. T., Barnum, C. J., Chang, J., Chung, J., Caspell-Garcia, C., Taylor, P., Mollenhauer, B., Schlossmacher, M. G., Ereshefsky, L., Yen, M., Kopil, C., Frasier, M., Marek, K., Hertzberg, V. S., & Tansey, M. G. (2017). Candidate inflammatory biomarkers display unique relationships with alpha-synuclein and correlate with measures of disease severity in subjects with Parkinson's disease. Journal of Neuroinflammation, 14(1), 164. https://doi.org/10.1186/s12974-017-0935-1
Eidson LN, et al. Candidate Inflammatory Biomarkers Display Unique Relationships With Alpha-synuclein and Correlate With Measures of Disease Severity in Subjects With Parkinson's Disease. J Neuroinflammation. 2017 Aug 18;14(1):164. PubMed PMID: 28821274.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Candidate inflammatory biomarkers display unique relationships with alpha-synuclein and correlate with measures of disease severity in subjects with Parkinson's disease. AU - Eidson,Lori N, AU - Kannarkat,George T, AU - Barnum,Christopher J, AU - Chang,Jianjun, AU - Chung,Jaegwon, AU - Caspell-Garcia,Chelsea, AU - Taylor,Peggy, AU - Mollenhauer,Brit, AU - Schlossmacher,Michael G, AU - Ereshefsky,Larry, AU - Yen,Mark, AU - Kopil,Catherine, AU - Frasier,Mark, AU - Marek,Kenneth, AU - Hertzberg,Vicki S, AU - Tansey,Malú G, Y1 - 2017/08/18/ PY - 2017/05/23/received PY - 2017/08/07/accepted PY - 2017/8/20/entrez PY - 2017/8/20/pubmed PY - 2018/5/8/medline KW - CSF KW - Daily rhythm KW - Inflammation KW - Parkinson’s disease KW - Protein biomarkers KW - Serum SP - 164 EP - 164 JF - Journal of neuroinflammation JO - J Neuroinflammation VL - 14 IS - 1 N2 - BACKGROUND: Efforts to identify fluid biomarkers of Parkinson's disease (PD) have intensified in the last decade. As the role of inflammation in PD pathophysiology becomes increasingly recognized, investigators aim to define inflammatory signatures to help elucidate underlying mechanisms of disease pathogenesis and aid in identification of patients with inflammatory endophenotypes that could benefit from immunomodulatory interventions. However, discordant results in the literature and a lack of information regarding the stability of inflammatory factors over a 24-h period have hampered progress. METHODS: Here, we measured inflammatory proteins in serum and CSF of a small cohort of PD (n = 12) and age-matched healthy control (HC) subjects (n = 6) at 11 time points across 24 h to (1) identify potential diurnal variation, (2) reveal differences in PD vs HC, and (3) to correlate with CSF levels of amyloid β (Aβ) and α-synuclein in an effort to generate data-driven hypotheses regarding candidate biomarkers of PD. RESULTS: Despite significant variability in other factors, a repeated measures two-way analysis of variance by time and disease state for each analyte revealed that serum IFNγ, TNF, and neutrophil gelatinase-associated lipocalin (NGAL) were stable across 24 h and different between HC and PD. Regression analysis revealed that C-reactive protein (CRP) was the only factor with a strong linear relationship between CSF and serum. PD and HC subjects showed significantly different relationships between CSF Aβ proteins and α-synuclein and specific inflammatory factors, and CSF IFNγ and serum IL-8 positively correlated with clinical measures of PD. Finally, linear discriminant analysis revealed that serum TNF and CSF α-synuclein discriminated between PD and HC with a minimum of 82% sensitivity and 83% specificity. CONCLUSIONS: Our findings identify a panel of inflammatory factors in serum and CSF that can be reliably measured, distinguish between PD and HC, and monitor inflammation as disease progresses or in response to interventional therapies. This panel may aid in generating hypotheses and feasible experimental designs towards identifying biomarkers of neurodegenerative disease by focusing on analytes that remain stable regardless of time of sample collection. SN - 1742-2094 UR - https://www.unboundmedicine.com/medline/citation/28821274/Candidate_inflammatory_biomarkers_display_unique_relationships_with_alpha_synuclein_and_correlate_with_measures_of_disease_severity_in_subjects_with_Parkinson's_disease_ L2 - https://jneuroinflammation.biomedcentral.com/articles/10.1186/s12974-017-0935-1 DB - PRIME DP - Unbound Medicine ER -