دورية أكاديمية
أعرض في EDS

α-Synuclein oligomers in skin biopsy of idiopathic and monozygotic twin patients with Parkinson's disease.

التفاصيل البيبلوغرافية
العنوان: α-Synuclein oligomers in skin biopsy of idiopathic and monozygotic twin patients with Parkinson's disease.
المؤلفون: Mazzetti S; Department of Biosciences, Università degli Studi di Milano, Milan, Italy.; Fondazione Grigioni per il Morbo di Parkinson, Milan, Italy., Basellini MJ; Department of Biosciences, Università degli Studi di Milano, Milan, Italy.; Fondazione Grigioni per il Morbo di Parkinson, Milan, Italy., Ferri V; Fondazione Grigioni per il Morbo di Parkinson, Milan, Italy.; Parkinson Institute, ASST 'Gaetano Pini-CTO', Milan, Italy., Cassani E; Fondazione Grigioni per il Morbo di Parkinson, Milan, Italy.; Parkinson Institute, ASST 'Gaetano Pini-CTO', Milan, Italy., Cereda E; Clinical Nutrition and Dietetics Unit, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy., Paolini M; Department of Biosciences, Università degli Studi di Milano, Milan, Italy., Calogero AM; Department of Biosciences, Università degli Studi di Milano, Milan, Italy.; Fondazione Grigioni per il Morbo di Parkinson, Milan, Italy., Bolliri C; Fondazione Grigioni per il Morbo di Parkinson, Milan, Italy.; Parkinson Institute, ASST 'Gaetano Pini-CTO', Milan, Italy., De Leonardis M; Department of Biosciences, Università degli Studi di Milano, Milan, Italy., Sacilotto G; Parkinson Institute, ASST 'Gaetano Pini-CTO', Milan, Italy., Cilia R; Parkinson Institute, ASST 'Gaetano Pini-CTO', Milan, Italy., Cappelletti G; Department of Biosciences, Università degli Studi di Milano, Milan, Italy.; Center of Excellence on Neurodegenerative Diseases, Università degli Studi di Milano, Milan, Italy., Pezzoli G; Fondazione Grigioni per il Morbo di Parkinson, Milan, Italy.; Parkinson Institute, ASST 'Gaetano Pini-CTO', Milan, Italy.
المصدر: Brain : a journal of neurology [Brain] 2020 Mar 01; Vol. 143 (3), pp. 920-931.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't; Twin Study
اللغة: English
بيانات الدورية: Publisher: Oxford University Press Country of Publication: England NLM ID: 0372537 Publication Model: Print Cited Medium: Internet ISSN: 1460-2156 (Electronic) Linking ISSN: 00068950 NLM ISO Abbreviation: Brain Subsets: MEDLINE
أسماء مطبوعة: Publication: Oxford : Oxford University Press
Original Publication: London.
مواضيع طبية MeSH: Immunoassay/*methods , Parkinson Disease/*metabolism , Skin/*metabolism , Synucleins/*metabolism , Twins, Monozygotic/*genetics, Autonomic Nervous System/metabolism ; Case-Control Studies ; Female ; Genetic Predisposition to Disease/genetics ; Humans ; Male ; Middle Aged ; Presynaptic Terminals/metabolism
مستخلص: A variety of cellular processes, including vesicle clustering in the presynaptic compartment, are impaired in Parkinson's disease and have been closely associated with α-synuclein oligomerization. Emerging evidence proves the existence of α-synuclein-related pathology in the peripheral nervous system, even though the presence of α-synuclein oligomers in situ in living patients remains poorly investigated. In this case-control study, we show previously undetected α-synuclein oligomers within synaptic terminals of autonomic fibres in skin biopsies by means of the proximity ligation assay and propose a procedure for their quantification (proximity ligation assay score). Our study revealed a significant increase in α-synuclein oligomers in consecutive patients with Parkinson's disease compared to consecutive healthy controls (P < 0.001). Proximity ligation assay score (threshold value > 96 using receiver operating characteristic) was found to have good sensitivity, specificity and positive predictive value (82%, 86% and 89%, respectively). Furthermore, to disclose the role of putative genetic predisposition in Parkinson's disease aetiology, we evaluated the differential accumulation of oligomers in a unique cohort of 19 monozygotic twins discordant for Parkinson's disease. The significant difference between patients and healthy subjects was confirmed in twins. Intriguingly, although no difference in median values was detected between consecutive healthy controls and healthy twins, the prevalence of healthy subjects positive for proximity ligation assay score was significantly greater in twins than in the consecutive cohort (47% versus 14%, P = 0.019). This suggests that genetic predisposition is important, but not sufficient, in the aetiology of the disease and strengthens the contribution of environmental factors. In conclusion, our data provide evidence that α-synuclein oligomers accumulate within synaptic terminals of autonomic fibres of the skin in Parkinson's disease for the first time. This finding endorses the hypothesis that α-synuclein oligomers could be used as a reliable diagnostic biomarker for Parkinson's disease. It also offers novel insights into the physiological and pathological roles of α-synuclein in the peripheral nervous system.
(© The Author(s) (2020). Published by Oxford University Press on behalf of the Guarantors of Brain.)
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فهرسة مساهمة: Keywords: Parkinson’s disease; monozygotic twins; proximity ligation assay; skin biopsy; α-synuclein oligomers
المشرفين على المادة: 0 (Synucleins)
تواريخ الأحداث: Date Created: 20200207 Date Completed: 20200706 Latest Revision: 20200706
رمز التحديث: 20221213
مُعرف محوري في PubMed: PMC7089656
DOI: 10.1093/brain/awaa008
PMID: 32025699
قاعدة البيانات: MEDLINE
الوصف
تدمد:1460-2156
DOI:10.1093/brain/awaa008