Efficient RT-QuIC seeding activity for α-synuclein in olfactory mucosa samples of patients with Parkinson’s disease and multiple system atrophy
Abstract 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 abnormal α-synuclein in brainstem while neurodegenerative parkinso...
| Main Authors: | , , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2019-08-01
|
| Series: | Translational Neurodegeneration |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s40035-019-0164-x |
| _version_ | 1818541891964108800 |
|---|---|
| author | 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 |
| author_facet | 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 |
| author_sort | Chiara Maria Giulia De Luca |
| collection | DOAJ |
| description | Abstract 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 abnormal α-synuclein in brainstem while neurodegenerative parkinsonisms might be associated with accumulation of either α-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 of α-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 recombinant α-synuclein as substrate of reaction, we have assessed the ability of OM collected from patients with clinical diagnoses of PD and MSA to induce α-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 induced α-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 for α-synuclein. Additional studies are required for (i) estimating sensitivity and specificity of the technique and for (ii) evaluating its application for the diagnosis of PD and neurodegenerative parkinsonisms. RT-QuIC analyses of OM and cerebrospinal fluid (CSF) can be combined with the aim of increasing the overall diagnostic accuracy of these diseases, especially in the early stages. |
| first_indexed | 2024-12-11T22:15:05Z |
| format | Article |
| id | doaj.art-03eb1f542ae049dcb9af8d246ca46cb9 |
| institution | Directory Open Access Journal |
| issn | 2047-9158 |
| language | English |
| last_indexed | 2024-12-11T22:15:05Z |
| publishDate | 2019-08-01 |
| publisher | BMC |
| record_format | Article |
| series | Translational Neurodegeneration |
| spelling | doaj.art-03eb1f542ae049dcb9af8d246ca46cb92022-12-22T00:48:37ZengBMCTranslational Neurodegeneration2047-91582019-08-018111410.1186/s40035-019-0164-xEfficient RT-QuIC seeding activity for α-synuclein in olfactory mucosa samples of patients with Parkinson’s disease and multiple system atrophyChiara Maria Giulia De Luca0Antonio Emanuele Elia1Sara Maria Portaleone2Federico Angelo Cazzaniga3Martina Rossi4Edoardo Bistaffa5Elena De Cecco6Joanna Narkiewicz7Giulia Salzano8Olga Carletta9Luigi Romito10Grazia Devigili11Paola Soliveri12Pietro Tiraboschi13Giuseppe Legname14Fabrizio Tagliavini15Roberto Eleopra16Giorgio Giaccone17Fabio Moda18Fondazione IRCCS Istituto Neurologico Carlo Besta, Unit of Neurology 5 and NeuropathologyFondazione IRCCS Istituto Neurologico Carlo Besta, Unit of Neurology I - Parkinson and Movement Disorders UnitDepartment of Health Sciences, Università degli Studi di Milano, Otolaryngology Unit, San Paolo HospitalFondazione IRCCS Istituto Neurologico Carlo Besta, Unit of Neurology 5 and NeuropathologyDepartment of Neuroscience, Scuola Internazionale Superiore di Studi Avanzati (SISSA), Laboratory of Prion BiologyFondazione IRCCS Istituto Neurologico Carlo Besta, Unit of Neurology 5 and NeuropathologyDepartment of Neuroscience, Scuola Internazionale Superiore di Studi Avanzati (SISSA), Laboratory of Prion BiologyDepartment of Neuroscience, Scuola Internazionale Superiore di Studi Avanzati (SISSA), Laboratory of Prion BiologyDepartment of Neuroscience, Scuola Internazionale Superiore di Studi Avanzati (SISSA), Laboratory of Prion BiologyFondazione IRCCS Istituto Neurologico Carlo Besta, Unit of Neurology 5 and NeuropathologyFondazione IRCCS Istituto Neurologico Carlo Besta, Unit of Neurology I - Parkinson and Movement Disorders UnitFondazione IRCCS Istituto Neurologico Carlo Besta, Unit of Neurology I - Parkinson and Movement Disorders UnitFondazione IRCCS Istituto Neurologico Carlo Besta, Unit of Neurology I - Parkinson and Movement Disorders UnitFondazione IRCCS Istituto Neurologico Carlo Besta, Unit of Neurology 5 and NeuropathologyDepartment of Neuroscience, Scuola Internazionale Superiore di Studi Avanzati (SISSA), Laboratory of Prion BiologyFondazione IRCCS Istituto Neurologico Carlo Besta, Scientific DirectorateFondazione IRCCS Istituto Neurologico Carlo Besta, Unit of Neurology I - Parkinson and Movement Disorders UnitFondazione IRCCS Istituto Neurologico Carlo Besta, Unit of Neurology 5 and NeuropathologyFondazione IRCCS Istituto Neurologico Carlo Besta, Unit of Neurology 5 and NeuropathologyAbstract 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 abnormal α-synuclein in brainstem while neurodegenerative parkinsonisms might be associated with accumulation of either α-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 of α-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 recombinant α-synuclein as substrate of reaction, we have assessed the ability of OM collected from patients with clinical diagnoses of PD and MSA to induce α-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 induced α-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 for α-synuclein. Additional studies are required for (i) estimating sensitivity and specificity of the technique and for (ii) evaluating its application for the diagnosis of PD and neurodegenerative parkinsonisms. RT-QuIC analyses of OM and cerebrospinal fluid (CSF) can be combined with the aim of increasing the overall diagnostic accuracy of these diseases, especially in the early stages.http://link.springer.com/article/10.1186/s40035-019-0164-xRT-QuICOlfactory mucosaParkinson’s diseaseNeurodegenerative parkinsonismsα-Synuclein |
| spellingShingle | 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 Efficient RT-QuIC seeding activity for α-synuclein in olfactory mucosa samples of patients with Parkinson’s disease and multiple system atrophy Translational Neurodegeneration RT-QuIC Olfactory mucosa Parkinson’s disease Neurodegenerative parkinsonisms α-Synuclein |
| title | Efficient RT-QuIC seeding activity for α-synuclein in olfactory mucosa samples of patients with Parkinson’s disease and multiple system atrophy |
| title_full | Efficient RT-QuIC seeding activity for α-synuclein in olfactory mucosa samples of patients with Parkinson’s disease and multiple system atrophy |
| title_fullStr | Efficient RT-QuIC seeding activity for α-synuclein in olfactory mucosa samples of patients with Parkinson’s disease and multiple system atrophy |
| title_full_unstemmed | Efficient RT-QuIC seeding activity for α-synuclein in olfactory mucosa samples of patients with Parkinson’s disease and multiple system atrophy |
| title_short | Efficient RT-QuIC seeding activity for α-synuclein in olfactory mucosa samples of patients with Parkinson’s disease and multiple system atrophy |
| title_sort | efficient rt quic seeding activity for α synuclein in olfactory mucosa samples of patients with parkinson s disease and multiple system atrophy |
| topic | RT-QuIC Olfactory mucosa Parkinson’s disease Neurodegenerative parkinsonisms α-Synuclein |
| url | http://link.springer.com/article/10.1186/s40035-019-0164-x |
| work_keys_str_mv | AT chiaramariagiuliadeluca efficientrtquicseedingactivityforasynucleininolfactorymucosasamplesofpatientswithparkinsonsdiseaseandmultiplesystematrophy AT antonioemanueleelia efficientrtquicseedingactivityforasynucleininolfactorymucosasamplesofpatientswithparkinsonsdiseaseandmultiplesystematrophy AT saramariaportaleone efficientrtquicseedingactivityforasynucleininolfactorymucosasamplesofpatientswithparkinsonsdiseaseandmultiplesystematrophy AT federicoangelocazzaniga efficientrtquicseedingactivityforasynucleininolfactorymucosasamplesofpatientswithparkinsonsdiseaseandmultiplesystematrophy AT martinarossi efficientrtquicseedingactivityforasynucleininolfactorymucosasamplesofpatientswithparkinsonsdiseaseandmultiplesystematrophy AT edoardobistaffa efficientrtquicseedingactivityforasynucleininolfactorymucosasamplesofpatientswithparkinsonsdiseaseandmultiplesystematrophy AT elenadececco efficientrtquicseedingactivityforasynucleininolfactorymucosasamplesofpatientswithparkinsonsdiseaseandmultiplesystematrophy AT joannanarkiewicz efficientrtquicseedingactivityforasynucleininolfactorymucosasamplesofpatientswithparkinsonsdiseaseandmultiplesystematrophy AT giuliasalzano efficientrtquicseedingactivityforasynucleininolfactorymucosasamplesofpatientswithparkinsonsdiseaseandmultiplesystematrophy AT olgacarletta efficientrtquicseedingactivityforasynucleininolfactorymucosasamplesofpatientswithparkinsonsdiseaseandmultiplesystematrophy AT luigiromito efficientrtquicseedingactivityforasynucleininolfactorymucosasamplesofpatientswithparkinsonsdiseaseandmultiplesystematrophy AT graziadevigili efficientrtquicseedingactivityforasynucleininolfactorymucosasamplesofpatientswithparkinsonsdiseaseandmultiplesystematrophy AT paolasoliveri efficientrtquicseedingactivityforasynucleininolfactorymucosasamplesofpatientswithparkinsonsdiseaseandmultiplesystematrophy AT pietrotiraboschi efficientrtquicseedingactivityforasynucleininolfactorymucosasamplesofpatientswithparkinsonsdiseaseandmultiplesystematrophy AT giuseppelegname efficientrtquicseedingactivityforasynucleininolfactorymucosasamplesofpatientswithparkinsonsdiseaseandmultiplesystematrophy AT fabriziotagliavini efficientrtquicseedingactivityforasynucleininolfactorymucosasamplesofpatientswithparkinsonsdiseaseandmultiplesystematrophy AT robertoeleopra efficientrtquicseedingactivityforasynucleininolfactorymucosasamplesofpatientswithparkinsonsdiseaseandmultiplesystematrophy AT giorgiogiaccone efficientrtquicseedingactivityforasynucleininolfactorymucosasamplesofpatientswithparkinsonsdiseaseandmultiplesystematrophy AT fabiomoda efficientrtquicseedingactivityforasynucleininolfactorymucosasamplesofpatientswithparkinsonsdiseaseandmultiplesystematrophy |