Abstract
BACKGROUND: Conflicting results have been published regarding the accumulation of alpha-synuclein (aSyn) pathology, in intestinal tissues of patients with Parkinson's disease (PD). This study investigates the use of a panel of aSyn antibodies for detecting pathological aSyn in rectal biopsy samples from PD patients and healthy individuals. MATERIALS AND METHODS: A panel of antibodies targeting native, phosphorylated and conformation-specific forms of aSyn was used to characterize aSyn distribution in the substantia nigra and colonic tissues of controls and individuals with Lewy pathology. Distribution of aSyn was further analyzed in formalin-fixed and paraffin-embedded (FFPE) submucosal rectal biopsies of 24 PD patients and 20 healthy controls. RESULTS: All tested antibodies valuably detected aSyn pathology in the PD substantia nigra. Native aSyn was observed at high levels in colonic tissue. The immunoreactive patterns of native aSyn, conformation-specific or phosphorylated aSyn in rectal biopsies did not show notable differences between PD patients and healthy subjects. CONCLUSION: The utility of immunohistochemical detection with currently commercially available antibodies for native and pathological forms of aSyn in rectal tissues appears limited. The findings advocate for the development of alternative methods to detect pathological aSyn conformers in rectal FFPE biopsies.