In Vivo Gastric Detection of a-Synuclein Inclusions in Parkinson’s Disease  Alvaro S anchez-Ferro, MD, 1,2,3,4 * Alberto R abano, MD, 5 Marıa Jos e Catal an, MD, 6 Fernando Canga Rodrıguez-Valc arcel, MD, 7 Servando Fern andez Dıez, MD, 8 Jaime Herreros-Rodrıguez, MD, 1,2 Elvira Garcıa-Cobos, MD, 9 Marina Mata  Alvarez-Santullano, MD, 9 Lydia L opez-Manzanares, MD, 9,10 Antonio J. Mosqueira, MD, 10 Lydia Vela Desojo, MD, 11 Juan Jos eL opez-Lozano, MD, 9 Eva L opez-Vald es, MD, 6 Rafael S anchez-S anchez, MD, 12 and Jos e Antonio Molina-Arjona, MD 1,2,4 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 Investigaci on Biom edica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain 5 Banco de Tejidos de la Fundaci  on CIEN, Alzheimer Center Reina Sofıa Foundation, Madrid, Spain 6 Movement Disorders Unit, Department of Neurology, Hospital Clınico San Carlos, Universidad Complutense de Madrid, Madrid, Spain 7 Department of Medicine Endoscopy Unit, Department of Gastroenterology, Hospital Universitario 12 de Octubre, Madrid, Spain 8 Endoscopy Unit, Department of Gastroenterology, Hospital Clınico San Carlos, Universidad Complutense de Madrid, Madrid, Spain 9 Movement Disorders Unit, Department of Neurology, Hospital Universitario Puerta del Hierro, Madrid, Spain 10 Movement Disorders Unit, Department of Neurology (L. L opez-Manzanares and A.J. Mosqueira), Hospital Univertario de la Princesa, Madrid, Spain 11 Department of Neurology, Fundaci on Hospital Alcorc on, Alcorc on, Madrid, Spain 12 Department of Pathology, Hospital Universitario Reina Sofıa, C ordoba, Spain ABSTRACT: a-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 gastros- copy in 28 patients with Parkinson’s disease and in 29 age- and sex-matched controls. Gastroscopy was per- formed to start enteral levodopa (L-dopa) therapy in cases and for diagnostic purposes in controls (gastro- esophageal 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 a-synuclein. The neuropathological diagnosis was established post hoc. No differences were found in the baseline charac- teristics of the groups. Positive fibers for the a- 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 presympto- matic parkinsonism.” Neuropathological diagnosis based on a-synuclein immunostaining showed a sensi- tivity 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 a-synuclein inclusions in the gastric mucosa is a useful and safe tool providing in vivo evi- dence of the underlying neurodegenerative peripheral ------------------------------------------------------------------------------------------------------------------------------ *Correspondence to:  Alvaro S anchez-Ferro, MD, Calle La Mas o 20, E-28034 Madrid, Spain, E-mail: asferro@mit.edu Funding agencies: This study was supported by grants from Instituto de Salud Carlos III and Fundaci  on 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 M1Vision Consor- tium (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 inter- pretation, 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. Revised: 9 September 2013; Revised: 9 September 2013; Accepted: 13 July 2014 Published online 00 Month 2014 in Wiley Online Library (wileyonlinelibrary.com). DOI: 10.1002/mds.25988 RESEARCH ARTICLE Movement Disorders, Vol. 00, No. 00, 2014 1