Get access

In vivo gastric detection of α-synuclein inclusions in Parkinson's disease

Authors

  • Álvaro Sánchez-Ferro MD,

    Corresponding author
    1. Department of Neurology, Hospital Universitario 12 de Octubre, Madrid, Spain
    2. Department of Medicine, Faculty of Medicine, Universidad Complutense de Madrid, Madrid, Spain
    3. Research Laboratory of Electronics, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA
    4. Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain
    • Correspondence to: Álvaro Sánchez-Ferro, MD, Calle La Masó 20, E-28034 Madrid, Spain, E-mail: asferro@mit.edu

    Search for more papers by this author
  • Alberto Rábano MD,

    1. Banco de Tejidos de la Fundación CIEN, Alzheimer Center Reina Sofía Foundation, Madrid, Spain
    Search for more papers by this author
  • María José Catalán MD,

    1. Movement Disorders Unit, Department of Neurology, Hospital Clínico San Carlos, Universidad Complutense de Madrid, Madrid, Spain
    Search for more papers by this author
  • Fernando Canga Rodríguez-Valcárcel MD,

    1. Department of Medicine Endoscopy Unit, Department of Gastroenterology, Hospital Universitario 12 de Octubre, Madrid, Spain
    Search for more papers by this author
  • Servando Fernández Díez MD,

    1. Endoscopy Unit, Department of Gastroenterology, Hospital Clínico San Carlos, Universidad Complutense de Madrid, Madrid, Spain
    Search for more papers by this author
  • Jaime Herreros-Rodríguez MD,

    1. Department of Neurology, Hospital Universitario 12 de Octubre, Madrid, Spain
    2. Department of Medicine, Faculty of Medicine, Universidad Complutense de Madrid, Madrid, Spain
    Search for more papers by this author
  • Elvira García-Cobos MD,

    1. Movement Disorders Unit, Department of Neurology, Hospital Universitario Puerta del Hierro, Madrid, Spain
    Search for more papers by this author
  • Marina Mata Álvarez-Santullano MD,

    1. Movement Disorders Unit, Department of Neurology, Hospital Universitario Puerta del Hierro, Madrid, Spain
    Search for more papers by this author
  • Lydia López-Manzanares MD,

    1. Movement Disorders Unit, Department of Neurology, Hospital Universitario Puerta del Hierro, Madrid, Spain
    2. Movement Disorders Unit, Department of Neurology (L. López-Manzanares and A.J. Mosqueira), Hospital Univertario de la Princesa, Madrid, Spain
    Search for more papers by this author
  • Antonio J. Mosqueira MD,

    1. Movement Disorders Unit, Department of Neurology (L. López-Manzanares and A.J. Mosqueira), Hospital Univertario de la Princesa, Madrid, Spain
    Search for more papers by this author
  • Lydia Vela Desojo MD,

    1. Department of Neurology, Fundación Hospital Alcorcón, Alcorcón, Madrid, Spain
    Search for more papers by this author
  • Juan José López-Lozano MD,

    1. Movement Disorders Unit, Department of Neurology, Hospital Universitario Puerta del Hierro, Madrid, Spain
    Search for more papers by this author
  • Eva López-Valdés MD,

    1. Movement Disorders Unit, Department of Neurology, Hospital Clínico San Carlos, Universidad Complutense de Madrid, Madrid, Spain
    Search for more papers by this author
  • Rafael Sánchez-Sánchez MD,

    1. Department of Pathology, Hospital Universitario Reina Sofía, Córdoba, Spain
    Search for more papers by this author
  • José Antonio Molina-Arjona MD

    1. Department of Neurology, Hospital Universitario 12 de Octubre, Madrid, Spain
    2. Department of Medicine, Faculty of Medicine, Universidad Complutense de Madrid, Madrid, Spain
    3. Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain
    Search for more papers by this author

  • Funding agencies: This study was supported by grants from Instituto de Salud Carlos III and Fundación Neurociencias y Envejecimiento, and the logistic support provided by Abbott Healthcare. Dr. Alvaro Sanchez-Ferro is currently enjoying a research fellowship grant from the Madrid-MIT M+Vision Consortium (Comunidad de Madrid).

  • Relevant conflicts of interest/financial disclosures: The sponsors of the study had no role in the study design, data collection, data analysis, data interpretation, or writing of the report. All authors had full access to all data and contributed to manuscript revision. The corresponding author wrote the first draft and had final responsibility for the decision to submit for publication.

  • Full financial disclosures and author roles may be found in the online version of this article.

Abstract

α-Synuclein inclusions have been identified in the brain and some parts of the enteric nervous system in Parkinson's disease cases. We aimed to assess these inclusions in gastric mucosa samples from patients with symptomatic Parkinson's disease. Random biopsies were performed by gastroscopy in 28 patients with Parkinson's disease and in 29 age- and sex-matched controls. Gastroscopy was performed to start enteral levodopa (l-dopa) therapy in cases and for diagnostic purposes in controls (gastroesophageal reflux, anemia, and abdominal pain were the main indications). The clinical definition of cases and controls was made a priori. Six controls had data suggestive of “mild presymptomatic parkinsonism”. Biopsy specimens were immunostained for α-synuclein. The neuropathological diagnosis was established post hoc. No differences were found in the baseline characteristics of the groups. Positive fibers for the α-synuclein protein were observed in 17 of 28 (60.7%) Parkinson's disease patients, 1 of 23 controls (4.3%), and 1 of 6 (16.7%) cases of incident “mild presymptomatic parkinsonism.” Neuropathological diagnosis based on α-synuclein immunostaining showed a sensitivity of 85% (95% confidence interval [CI] 62.1-96.8), specificity of 95% (95% CI 76.2-99.9) and area under the receiver operating characteristics curve (AUC) of 0.90 (95% CI 0.80-1.00). No adverse events occurred. Detection of α-synuclein inclusions in the gastric mucosa is a useful and safe tool providing in vivo evidence of the underlying neurodegenerative peripheral involvement linked to Parkinson's disease. Further studies are warranted to determine its pathophysiological implications. © 2014 International Parkinson and Movement Disorder Society

Ancillary