Lipopolysaccharide-binding protein and future Parkinson’s disease risk: a European prospective cohort

Journal of Neuroinflammation

Research

Lefkos Middleton¹  Elio Riboli²  María-Dolores Chirlaque³  Marcela Guevara⁴  Pilar Amiano⁵  Giovanna Masala⁶  Gary W. Miller⁷  Brismar Pinto-Pacheco⁸  Brooklyn McNeil⁸  Alicia K. Heath⁹  Bastiaan R. Bloem^1,10  Sirwan K. L. Darweesh^1,10  Myrthe Frissen^1,10  Maurizio Zibetti^1,11  Salvatore Panico^1,12  Rudolf Kaaks^1,13  Verena Katzke^1,13  Sabina Sieri^1,14  Maria-Jose Sánchez^1,15  Dafina Petrova^1,15  Douglas I. Walker^1,16  Yujia Zhao^1,17  Susan Peters^1,18  Roel Vermeulen^1,19  Christina M. Lill^2,20  Mazda Jenab^2,21  Raul Zamora-Ros^2,22 

[1] Ageing Epidemiology Research Unit (AGE), School of Public Health, Imperial College London, London, UK;Public Health Directorate, Imperial College NHS Healthcare Trust, London, UK;Cancer Epidemiology and Prevention Research Unit, School of Public Health, Imperial College London, London, UK;Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain;Department of Epidemiology, Regional Health Council, IMIB-Arrixaca, Murcia University, Murcia, Spain;Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain;Instituto de Salud Pública y Laboral de Navarra, Pamplona, Spain;Navarra Institute for Health Research (IdiSNA), Pamplona, Spain;Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain;Sub Directorate for Public Health and Addictions of Gipuzkoa, Ministry of Health of the Basque Government, San Sebastián, Spain;Epidemiology of Chronic and Communicable Diseases Group, Biodonostia Health Research Institute, San Sebastián, Spain;Clinical Epidemiology Unit, Institute for Cancer Research, Prevention and Clinical Network (ISPRO), Florence, Italy;Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University, New York, USA;Department of Environmental Medicine and Public Health, Icahn School of Medicine, Mount Sinai, New York, USA;Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK;Department of Neurology, Donders Institute for Brain, Cognition and Behaviour, Center of Expertise for Parkinson & Movement Disorders, Radboud University Medical Center, Nijmegen, The Netherlands;Department of Neuroscience “Rita Levi Montalcini”, University of Turin, Turin, Italy;SC Neurologia 2U, AOU Città Della Salute E Della Scienza, Turin, Italy;Dipartimento di Medicina Clinica e Chirurgia, Federico II University, Naples, Italy;Division of Cancer Epidemiology C020, German Cancer Research Center (DKFZ), Heidelberg, Germany;Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milan, Italy;Escuela Andaluza de Salud Pública, Granada, Spain;Instituto de Investigación Biosanitaria Ibs.GRANADA, Granada, Spain;Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain;Gangarosa Department of Environmental Health, Rollins School of Public Health, Emory University, Atlanta, USA;Institute for Risk Assessment Sciences, Utrecht University, Nieuw Gildestein, Room 3.53, Yalelaan 2, 3584 CM, Utrecht, The Netherlands;Institute for Risk Assessment Sciences, Utrecht University, Nieuw Gildestein, Room 3.53, Yalelaan 2, 3584 CM, Utrecht, The Netherlands;Institute for Risk Assessment Sciences, Utrecht University, Nieuw Gildestein, Room 3.59, Yalelaan 2, 3584 CM, Utrecht, The Netherlands;Institute for Risk Assessment Sciences, Utrecht University, Nieuw Gildestein, Room 3.53, Yalelaan 2, 3584 CM, Utrecht, The Netherlands;University Medical Centre Utrecht, Utrecht, The Netherlands;Institute of Epidemiology and Social Medicine, University of Münster, Münster, Germany;Ageing Epidemiology Research Unit (AGE), School of Public Health, Imperial College London, London, UK;Nutrition and Metabolism (NME) Branch, International Agency for Research on Cancer (IARC-WHO), Lyon, France;Unit of Nutrition and Cancer, Cancer Epidemiology Research Programme, Catalan Institute of Oncology (ICO), Bellvitge Biomedical Research Institute (IDIBELL), L’Hospitalet de Llobregat, Barcelona, Spain;

关键词: Parkinson’s disease;    Lipopolysaccharide-binding protein;    Pre-diagnostic;    Systemic inflammation;    Endotoxemia;   

DOI  :  10.1186/s12974-023-02846-2

 received in 2023-05-29, accepted in 2023-07-02,  发布年份 2023

来源: Springer

【 摘 要 】

IntroductionLipopolysaccharide (LPS) is the outer membrane component of Gram-negative bacteria. LPS-binding protein (LBP) is an acute-phase reactant that mediates immune responses triggered by LPS and has been used as a blood marker for LPS. LBP has recently been indicated to be associated with Parkinson’s disease (PD) in small-scale retrospective case–control studies. We aimed to investigate the association between LBP blood levels with PD risk in a nested case–control study within a large European prospective cohort.MethodsA total of 352 incident PD cases (55% males) were identified and one control per case was selected, matched by age at recruitment, sex and study center. LBP levels in plasma collected at recruitment, which was on average 7.8 years before diagnosis of the cases, were analyzed by enzyme linked immunosorbent assay. Odds ratios (ORs) were estimated for one unit increase of the natural log of LBP levels and PD incidence by conditional logistic regression.ResultsPlasma LBP levels were higher in prospective PD cases compared to controls (median (interquartile range) 26.9 (18.1–41.0) vs. 24.7 (16.6–38.4) µg/ml). The OR for PD incidence per one unit increase of log LBP was elevated (1.46, 95% CI 0.98–2.19). This association was more pronounced among women (OR 2.68, 95% CI 1.40–5.13) and overweight/obese subjects (OR 1.54, 95% CI 1.09–2.18).ConclusionThe findings suggest that higher plasma LBP levels may be associated with an increased risk of PD and may thus pinpoint to a potential role of endotoxemia in the pathogenesis of PD, particularly in women and overweight/obese individuals.

【 授权许可】

CC BY   
© The Author(s) 2023

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