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

Alpha-synuclein in the stomach... 

Mov Disord. 2014 Aug 11. doi: 10.1002/mds.25988. [Epub ahead of print]

Sánchez-Ferro A, Rábano A, Catalán MJ, Rodríguez-Valcárcel FC, Díez SF, Herreros-Rodríguez J, García-Cobos E, Alvarez-Santullano MM, López-Manzanares L, Mosqueira AJ, Desojo LV, López-Lozano JJ, López-Valdés E, Sánchez-Sánchez R, Molina-Arjona JA.

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.