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Original research
Environmental exposure to phthalates and dementia with Lewy bodies: contribution of metabolomics
  1. Arnaud Agin1,2,
  2. Frédéric Blanc1,3,
  3. Olivier Bousiges4,
  4. Claire Villette5,
  5. Nathalie Philippi1,3,
  6. Catherine Demuynck3,
  7. Catherine Martin-Hunyadi3,
  8. Benjamin Cretin1,3,
  9. Sabine Lang5,
  10. Julie Zumsteg5,
  11. Izzie Jacques Namer1,2,
  12. Dimitri Heintz5
  1. 1 ICube laboratory, UMR 7357, team IMIS and platform IRIS, University of Strasbourg, CNRS, FMTS (Fédération de Médicine Translationnelle de Strasbourg, Strasbourg, France
  2. 2 Nuclear Medicine and Molecular Imaging Department, ICANS (Institut de Cancérologie Strasbourg Europe), Strasbourg, France
  3. 3 Geriatrics Department, CM2R (Memory Resource and Research Centre), Day Hospital & Neurology Service, Neuropsychology Unit, University Hospital of Strasbourg, Strasbourg, France
  4. 4 Laboratory of Biochemistry and Molecular Biology, University Hospital of Strasbourg, Strasbourg, France
  5. 5 Institut de Biologie Moléculaire des Plantes, Plant Imaging and Mass Spectrometry (PIMS), CNRS, University of Strasbourg, Strasbourg, France
  1. Correspondence to Dr Arnaud Agin, Institut de Physique Biologique, Faculté de Médecine, Laboratoire ICube, Strasbourg 67085, France; agin{at}


Background In neurodegenerative diseases, alongside genetic factors, the possible intervention of environmental factors in the pathogenesis is increasingly being considered. In particular, recent evidence suggests the intervention of a pesticide-like xenobiotic in the initiation of disease with Lewy bodies (DLB).

Objectives To test for the presence of pesticides or other xenobiotics in the cerebrospinal fluid (CSF) of patients with DLB.

Methods A total of 45 patients were included in this study: 16 patients with DLB at the prodromal stage, 8 patients with DLB at the demented stage, 8 patients with Alzheimer’s disease (AD) at the prodromal stage and 13 patients with AD at the demented stage. CSF was obtained by lumbar puncture and analysed by liquid chromatography–mass spectrometry.

Results Among the compounds detected in greater abundance in the CSF of patients with DLB compared with patients with AD, only one had a xenobiotic profile potentially related to the pathophysiology of DLB. After normalisation and scaling, bis(2-ethylhexyl) phthalate was more abundant in the CSF of patients with DLB (whole cohort: 2.7-fold abundant in DLB, p=0.031; patients with dementia: 3.8-fold abundant in DLB, p=0.001).

Conclusions This study is the first reported presence of a phthalate in the CSF of patients with DLB. This molecule, which is widely distributed in the environment and enters the body orally, nasally and transdermally, was first introduced in the 1920s as a plasticizer. Thereafter, the first cases of DLB were described in the 1960s and 1970s. These observations suggest that phthalates may be involved in the pathophysiology of DLB.

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  • Contributors AA, FB, OB and DH contributed to the planning, conduct and reporting of the work described in the article. CV contributed to the conduct and reporting of the work described in the article. NP, CD, CM-H, BC, SL and JZ contributed to the conduct of the work described in the article. IJN contributed to the planning of the work described in the article.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests None declared.

  • Patient consent for publication Not required.

  • Ethics approval This study involves human participants. CPP Est IV (France) approved this study, with the ID Eudract 2012-A00992-41/HUS 5330. This study does not involve animal subjects.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement Data are available upon reasonable request. The data are available from Arnaud Agin, corresponding author.