| α-Synuclein in the ENS | Studies have detected phosphorylated alpha-synuclein in the colonic mucosa of patients with PD, even in early disease stages and in prodromal cases. |
| REM Sleep Behavior Disorder (RBD) | Patients with isolated RBD, a prodromal PD marker, frequently show gastrointestinal abnormalities and reduced vagal tone. |
| Gut Microbiota Alterations | Changes in gut microbiota composition have been documented in PD and may contribute to alpha-synuclein misfolding and aggregation in the ENS. |
| Appendiceal Evidence | Recent studies have identified the appendix as a potential reservoir for alpha-synuclein pathology, with appendectomy associated with altered PD risk in some populations. |
| Olfactory Dysfunction | Olfactory impairment is one of the earliest prodromal signs of PD and may precede motor symptoms by years. |
| Olfactory Bulb Pathology | Alpha-synuclein inclusions are frequently found in the olfactory bulb of PD patients, even in early disease stages. |
| Incidental Lewy Body Disease | Some individuals show Lewy body pathology in the brain at autopsy without clinical PD, suggesting that the pathological process can begin in the brain without obvious peripheral involvement. |
| Different Prodromal Phenotypes | Not all prodromal PD patients develop gastrointestinal symptoms early, supporting the existence of non-gut-first trajectories. |
| Databases | OMIMOrphanetClinicalTrialsPubMed |
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