Individuazione di nuovi biomarker nella Malattia di Parkinson: uno studio su biopsie gastrointestinali

In Parkinson’s Disease (PD), several evidence indicates the involvement of gut-brain axis as one of the primary physio-pathological mechanisms underlying α-Syn aggregation and following propagation to CNS. In this regard, pathological α-Syn may be a candidate PD biomarker for its role in PD pathophysiology and its expression in several peripheral tissues, most importantly in enteric nervous system. Furthermore, gastrointestinal dysfunctions represent one of the main non-motor symptoms in PD, often preceding the development of proper motor symptoms. Our aim was to investigate as ne biomarker α-Syn aggregation through specific antibodies and seeding activity in stomach-duodenum biopsies of PD patients by real-time quaking induced conversion (RT-QuIC) assay. The αSyn RT-QuIC assay follow the seeded aggregation of monomeric αSyn into amyloid fibrils upon seeding by traces of αSyn aggregates present in biospecimens. Real-Time Quaking-Induced Conversion (RT-QuIC) is an ultrasensitive technique originally introduced for prion diseases diagnosis that can detect minute amounts of amyloidogenic proteins in cerebrospinal fluid (CSF) or other biospecimens, taking advantage of their ability to trigger a protein self-aggregation. Recently, the assay was successfully adapted to detect α-Syn seeds in biofluid and tissues in patients with PD. We found a relevant α-Syn aggregated protein with 5G4 antibody and seeding activity in almost all biopsies of PD patients, with higher response in the duodenum biopsies than stomach and minimum activity were detected in the control biopsies. The enteric nervous system could be one of the earliest implicated structures in the processes of α-Syn aggregation and an unmet clinical need is a reliable early diagnostic biomarker for Parkinson’s disease. We suggest that the combination of endoscopic biopsy of the gastric and duodenal mucosa to the high sensitivity of the 5G4 IHC and RT-QuIC assay in the detection of α-Syn seeding activity could to be an helpful new biomarker to evaluate early stages of PD. In conclusion, our data suggest that duodenal biopsy may represent a safe, feasible and useful tool for characterizing PD GI pathology and discerning patients from controls. Future studies will be required to confirm these findings in in a prodromal or early PD phase and to evaluate subjects with other synucleinopathies in particular multiple system atrophy.