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Efficient RT-QuIC seeding activity for α-synuclein in olfactory mucosa samples of patients with Parkinson’s disease and multiple system atrophy

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Translational Neurodegeneration 2019年第1期8卷 290-303页

作者： Chiara Maria Giulia De Luca Antonio Emanuele Elia Sara Maria Portaleone Federico Angelo Cazzaniga Martina Rossi Edoardo Bistaffa Elena De Cecco Joanna Narkiewicz Giulia Salzano Olga Carletta Luigi Romito Grazia Devigili Paola Soliveri Pietro Tiraboschi Giuseppe Legname Fabrizio Tagliavini Roberto Eleopra Giorgio Giaccone fabio moda Fondazione IRCCS Istituto Neurologico Carlo Besta Unit of Neurology 5 and NeuropathologyMilanItaly Fondazione IRCCS Istituto Neurologico Carlo Besta Unit of Neurology I-Parkinson and Movement Disorders UnitMilanItaly Department of Health Sciences Universitàdegli Studi di MilanoOtolaryngology UnitSan Paolo HospitalMilanItaly Department of Neuroscience Scuola Internazionale Superiore di Studi Avanzati(SISSA)Laboratory of Prion BiologyTriesteItaly Fondazione IRCCS Istituto Neurologico Carlo Besta Scientific DirectorateMilanItaly

Background:Parkinson’s disease(PD)is a neurodegenerative disorder whose diagnosis is often challenging because symptoms may overlap with neurodegenerative parkinsonisms.PD is characterized by intraneuronal accumulation of abnormalα-synuclein in brainstem while neurodegenerative parkinsonisms might be associated with accumulation of eitherα-synuclein,as in the case of Multiple System Atrophy(MSA)or tau,as in the case of Corticobasal Degeneration(CBD)and Progressive Supranuclear Palsy(PSP),in other disease-specific brain regions.Definite diagnosis of all these diseases can be formulated only neuropathologically by detection and localization ofα-synuclein or tau aggregates in the brain.Compelling evidence suggests that trace-amount of these proteins can appear in peripheral tissues,including receptor neurons of the olfactory mucosa(OM).Methods:We have set and standardized the experimental conditions to extend the ultrasensitive Real Time Quaking Induced Conversion(RT-QuIC)assay for OM analysis.In particular,by using human recombinantα-synuclein as substrate of reaction,we have assessed the ability of OM collected from patients with clinical diagnoses of PD and MSA to induceα-synuclein aggregation,and compared their seeding ability to that of OM samples collected from patients with clinical diagnoses of CBD and PSP.Results:Our results showed that a significant percentage of MSA and PD samples inducedα-synuclein aggregation with high efficiency,but also few samples of patients with the clinical diagnosis of CBD and PSP caused the same effect.Notably,the final RT-QuIC aggregates obtained from MSA and PD samples owned peculiar biochemical and morphological features potentially enabling their discrimination.Conclusions:Our study provide the proof-of-concept that olfactory mucosa samples collected from patients with PD and MSA possess important seeding activities forα-synuclein.Additional studies are required for(i)estimating sensitivity and specificity of the technique and for(ii)evaluating its application for the diagno

关键词： RT-QuIC Olfactory mucosa Parkinson’s disease Neurodegenerative parkinsonisms α-Synuclein

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