Seed Amplification Assay-Based Detection of Alpha-Synuclein Aggregates Outperforms Immunohistochemical Analysis in the Intestinal Mucosal Biopsies of Parkinson's Disease and Multiple System Atrophy Participants

Seed amplification assay detects seeding-competent α-synuclein aggregates in Parkinson’s disease intestinal biopsies with high observed specificity (97.5–100%) and region-dependent sensitivity.

• Why it matters: Immunohistochemistry may miss seeding-competent pathology, and it is unclear whether intestinal α-synuclein seeding varies by gut region or tracks Parkinson’s disease progression.
• What they did: In a cross-sectional diagnostic accuracy study, duodenum, ileum, and sigmoid biopsies from Parkinson’s disease participants and age- and sex-matched healthy controls were tested by α-synuclein seed amplification assay and compared with proteinase K-resistant phospho-Ser129 immunohistochemistry.
• The result: In paired sigmoid samples, seed amplification assay detected aggregates 2.8-fold more frequently than immunohistochemistry, and sigmoid positivity increased with disease duration (40.00% at 10 years) while ileal positivity stayed stable; in multiple system atrophy, seeding activity appeared in all five MSA-P but not in two MSA-C.

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