@article{fenyi_detection_2019,
	title = {Detection of alpha-synuclein aggregates in gastrointestinal biopsies by protein misfolding cyclic amplification},
	volume = {129},
	issn = {0969-9961},
	url = {http://www.sciencedirect.com/science/article/pii/S0969996119301172},
	doi = {10.1016/j.nbd.2019.05.002},
	abstract = {Lewy bodies and neurites, the pathological signatures found in the central nervous system of Parkinson's disease ({PD}) patients, are primarily composed of aggregated alpha-synuclein ({aSyn}). The observation that {aSyn} aggregates are also found in the enteric nervous system has prompted several studies aimed at developing a diagnostic procedure based on the detection of pathological {aSyn} in gastrointestinal ({GI}) biopsies. The existing studies, which have all used immunohistochemistry for the detection of pathological {aSyn}, have had conflicting results. In the current survey, we analyzed the seeding propensity of {aSyn} aggregates from {GI} biopsies. A total of 29 subjects participated to this study, 18 {PD} patients and 11 controls. For each patient, 2 to 4 {GI} biopsies were taken from the same site (antrum, sigmoid colon or rectum) and used to seed the aggregation of recombinant {aSyn} in an assay inspired from the protein misfolding cyclic amplification ({PMCA}) method. In a subset of patients and controls (14 and 3, respectively), one or two additional biopsies were analyzed by immunohistochemistry for the presence of phosphorylated {aSyn} histopathology ({PASH}) using antibodies against phosphorylated {aSyn} and {PGP} 9.5. Except for one subject, none of the control samples seeded {aSyn} aggregation in {PMCA} reaction. {GI} biopsies from patients with {PD} seeded {aSyn} aggregation in 10 out of 18 cases (7 from the sigmoid colon, 2 from the antrum and one from the rectum). There was good agreement between {PMCA} and immunohistochemistry results as, except for two cases, all {PMCA}-positive {PD} patients were also {PASH}-positive. Our findings show that the {PMCA} method we implemented is capable of detecting {aSyn} aggregates in routine {GI} biopsies. They also suggest that rectum biopsies do not contain sufficient amounts of aggregated {aSyn} to detect seeded assembly by {PMCA}. While encouraging, our findings indicate that further studies are needed to establish the diagnostic potential of the {PMCA} method we implemented to detect {aSyn} aggregates in upper {GI} biopsies.},
	pages = {38--43},
	journaltitle = {Neurobiology of Disease},
	shortjournal = {Neurobiology of Disease},
	author = {Fenyi, Alexis and Leclair-Visonneau, Laurène and Clairembault, Thomas and Coron, Emmanuel and Neunlist, Michel and Melki, Ronald and Derkinderen, Pascal and Bousset, Luc},
	urldate = {2019-12-02},
	date = {2019-09-01},
	langid = {english},
	keywords = {Alpha-synuclein, Biopsy, Enteric nervous system, Gut, Parkinson's disease, Protein misfolding cyclic amplification, highlight, peer-reviewed},
}