Gastrointestinal Biopsy Obtained During Cancer Screening, a Biological Marker for alpha-Synucleinopathy?

The hallmark alteration in alpha-synucleinopathies, alpha-synuclein, is observed not only in the brain but also in the peripheral tissues, particularly in the intestine. This suggests that endoscopic biopsies performed for colon cancer screening could facilitate the assessment of alpha-synuclein in the gastrointestinal (GI) tract. Using immunohistochemistry for alpha-synuclein, we assessed whether GI biopsies could be used to confirm an ongoing alpha-synucleinopathy. Seventy-four subjects with cerebral alpha-synucleinopathy in various Braak stages with concomitant GI biopsies were available for study. In 81% of the subjects, alpha-synuclein was seen in the mucosal/submucosal GI biopsies. Two subjects with severe cerebral alpha-synucleinopathy and a long delay between biopsy and death displayed no alpha-synuclein pathology in the gut, and 11 subjects with sparse cerebral alpha-synucleinopathy displayed GI alpha-synuclein up to 36 years prior to death. The finding that there was no GI alpha-synuclein in 19% of the subjects with cerebral alpha-synucleinopathy, and alpha-synuclein was observed in the gut of 11 subjects (15%) with sparse cerebral alpha-synucleinopathy even many years prior to death is unexpected and jeopardizes the use of assessment of alpha-synuclein in the peripheral tissue for confirmation of an ongoing cerebral alpha-synucleinopathy.

Automated summary

This study investigated the use of GI biopsies to confirm ongoing alpha-synucleinopathy. The results showed that 81% of subjects had alpha-synuclein in the GI biopsies, and 15% of subjects with sparse cerebral alpha-synucleinopathy displayed GI alpha-synuclein even many years prior to death. This raises questions about the reliability of assessing alpha-synuclein in peripheral tissue for confirming ongoing cerebral alpha-synucleinopathy.