Duodenal alpha-Synuclein pathology and enteric gliosis in advanced Parkinson’s Disease patients
Bibliographic record
Abstract
ABSTRACT Background The role of the gut-brain axis has been recently highlighted as a major contributor to Parkinson’s Disease (PD) physiopathology, with numerous studies investigating bidirectional transmission of pathological protein aggregates, such as α-Synuclein (αSyn), in the context of neurodegenerative disease. However, little and often conflictual evidence is available from human studies due to patient heterogeneity, sampling variability, and the employment of antibodies with affinity for different αSyn epitopes. Objectives We aimed to investigate the enteric nervous system (ENS) in PD by characterizing αSyn alterations and glial responses in duodenum biopsies of PD patients by employing topography-specific sampling and conformation-specific αSyn antibodies. Methods 18 Patients with symptomatic PD who underwent Duodopa Percutaneous Endoscopic Gastrostomy and Jejunal Tube (PEG-J) procedure, as well as 18 age- and -sex-matched Healthy Control subjects undergoing routine diagnostic endoscopy, were included in the study. A mean of 4 duodenal wall biopsies were sampled from each patient. Immunohistochemistry was performed for anti-aggregated αSyn (5G4) and GFAP antibodies. Morphometrical-semi-quantitative analysis was performed to characterize αSyn-5G4+ and GFAP+ density and size. Results Elevated immunoreactivity for aggregated α-Syn was identified in all biopsies of PD patients compared to controls. αSyn-5G4+ colocalized with neuronal marker β-III-tubulin. Evaluation of enteric glia cells revealed an increased size and density when compared with controls, suggesting reactive gliosis. Conclusions Duodenal biopsy may represent a feasible and reliable tool for characterizing PD pathology in the GI tract and discerning patients from controls. Future studies are required to confirm these findings in a prodromal or early PD phase.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".