Alpha-synuclein distribution and seeding activity in rectal biopsies in Parkinson’s disease
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Background
Parkinson’s disease (PD) is characterized by the accumulation of alpha-synuclein (aSyn) pathology, not only in the brain but also in the intestinal tissues. This study investigates the use of unique aSyn antibodies and an aSyn seed amplification assay (SAA) for detecting pathological aSyn in rectal biopsy samples from PD patients and healthy individuals. These samples were preserved using formalin-fixed and paraffin-embedded (FFPE) methods.
Materials and Methods
The study analyzed the seeding capacity of FFPE submucosal rectal biopsies from 24 PD patients and 20 healthy controls using an aSyn SAA. It examined the distribution of aSyn using immunohistochemistry with antibodies targeting specific conformations and phosphorylated forms of aSyn at S129 and Y39. Additionally, the proximity-ligation assay was employed for phosphorylated S129 aSyn.
Results
Pathological forms of aSyn were found in all FFPE biopsies from PD patients, as confirmed by SAA, and these were linked to the severity of motor symptoms (MDS-UPDRS-III). However, the immunoreactive patterns of conformation-specific or phosphorylated aSyn in rectal biopsies did not show notable differences between PD patients and healthy subjects.
Conclusion
Pathological aSyn strains are detectable in FFPE rectal biopsies from PD patients with high accuracy using aSyn-SAA. However, the utility of immunohistochemical detection with current antibodies for identifying pathological aSyn forms appears limited. The findings advocate for the use of aSyn-SAA as a diagnostic tool for PD, contributing to a deeper understanding of the gut-brain connection in the disease.
