Validation of α-synuclein in L1CAM-immunocaptured exosomes as a biomarker for the stratification of Parkinsonian syndromes
<p><strong>Background:</strong> Parkinson’s disease is characterised by intraneuronal α-synuclein aggregation. Currently there is no α-synuclein-based blood test in clinical practice.</p> <p><strong>Objectives:</strong> Our aim was to assess by means of fur...
| Main Authors: | , , , , , , , |
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| Formato: | Journal article |
| Idioma: | English |
| Publicado: |
Wiley
2021
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| _version_ | 1826279351694393344 |
|---|---|
| author | Jiang, C Hopfner, F Berg, D Hu, M Pilotto, A Borroni, B Davis, JJ Tofaris, G |
| author_facet | Jiang, C Hopfner, F Berg, D Hu, M Pilotto, A Borroni, B Davis, JJ Tofaris, G |
| author_sort | Jiang, C |
| collection | OXFORD |
| description | <p><strong>Background:</strong> Parkinson’s disease is characterised by intraneuronal α-synuclein aggregation.
Currently there is no α-synuclein-based blood test in clinical practice.</p>
<p><strong>Objectives:</strong> Our aim was to assess by means of further testing and analysis whether α-synuclein
measurements in serum L1CAM-immunocaptured exosomes can differentiate Parkinson’s disease from related movement disorders.</p>
<p><strong>Methods:</strong> We used poly(carboxybetaine-methacrylate) coated magnetic beads to isolate L1CAMpositive exosomes and triplexed electrochemiluminescence to measure exosomal a-synuclein, clusterin and syntenin-1 from 267 serum samples. Combined analysis of our current and previously
published data from Oxford, Kiel, Brescia and PROSPECT cohorts consisting of individuals (total n=735) with Parkinson’s disease (PD, n=290), Multiple system atrophy (MSA, n=50), Progressive supranuclear palsy (PSP, n=116), Corticobasal syndrome (CBS, n=88) and healthy controls (HC,
n=191) was done using two-stage (training vs validation) ROC analysis.</p>
<p><strong>Results:</strong> We established that α-synuclein levels in L1CAM-immunocaptured exosomes above 14
pg/mL is a robust biomarker across cohorts that distinguishes Parkinson’s disease from MSA (AUC=0.90 vs 0.98) or four-repeat tauopathies (AUC=0.93 vs 0.94). We confirmed that exosomal clusterin is elevated in subjects with four-repeat tauopathy and when combined with α-synuclein it
improved the performance of the assay in differentiating Parkinson’s disease from four-repeat tauopathies to AUC=0.98 vs 0.99. Correction for the generic exosomal protein syntenin-1 did not consistently improve the performance of the assay.</p>
<p><strong>Conclusions:</strong> α-Synuclein and clusterin in L1CAM-immunocaptured serum exosomes is a validated
blood test for the molecular stratification of neuronal α-synucleinopathy (i.e. Lewy body pathology)
versus phenotypically related neurodegenerative movement disorders.</p> |
| first_indexed | 2024-03-06T23:57:24Z |
| format | Journal article |
| id | oxford-uuid:74b75d8f-da94-4ee4-ab94-b15ce000d257 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T23:57:24Z |
| publishDate | 2021 |
| publisher | Wiley |
| record_format | dspace |
| spelling | oxford-uuid:74b75d8f-da94-4ee4-ab94-b15ce000d2572022-03-26T20:04:46ZValidation of α-synuclein in L1CAM-immunocaptured exosomes as a biomarker for the stratification of Parkinsonian syndromesJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:74b75d8f-da94-4ee4-ab94-b15ce000d257EnglishSymplectic ElementsWiley2021Jiang, CHopfner, FBerg, DHu, MPilotto, ABorroni, BDavis, JJTofaris, G<p><strong>Background:</strong> Parkinson’s disease is characterised by intraneuronal α-synuclein aggregation. Currently there is no α-synuclein-based blood test in clinical practice.</p> <p><strong>Objectives:</strong> Our aim was to assess by means of further testing and analysis whether α-synuclein measurements in serum L1CAM-immunocaptured exosomes can differentiate Parkinson’s disease from related movement disorders.</p> <p><strong>Methods:</strong> We used poly(carboxybetaine-methacrylate) coated magnetic beads to isolate L1CAMpositive exosomes and triplexed electrochemiluminescence to measure exosomal a-synuclein, clusterin and syntenin-1 from 267 serum samples. Combined analysis of our current and previously published data from Oxford, Kiel, Brescia and PROSPECT cohorts consisting of individuals (total n=735) with Parkinson’s disease (PD, n=290), Multiple system atrophy (MSA, n=50), Progressive supranuclear palsy (PSP, n=116), Corticobasal syndrome (CBS, n=88) and healthy controls (HC, n=191) was done using two-stage (training vs validation) ROC analysis.</p> <p><strong>Results:</strong> We established that α-synuclein levels in L1CAM-immunocaptured exosomes above 14 pg/mL is a robust biomarker across cohorts that distinguishes Parkinson’s disease from MSA (AUC=0.90 vs 0.98) or four-repeat tauopathies (AUC=0.93 vs 0.94). We confirmed that exosomal clusterin is elevated in subjects with four-repeat tauopathy and when combined with α-synuclein it improved the performance of the assay in differentiating Parkinson’s disease from four-repeat tauopathies to AUC=0.98 vs 0.99. Correction for the generic exosomal protein syntenin-1 did not consistently improve the performance of the assay.</p> <p><strong>Conclusions:</strong> α-Synuclein and clusterin in L1CAM-immunocaptured serum exosomes is a validated blood test for the molecular stratification of neuronal α-synucleinopathy (i.e. Lewy body pathology) versus phenotypically related neurodegenerative movement disorders.</p> |
| spellingShingle | Jiang, C Hopfner, F Berg, D Hu, M Pilotto, A Borroni, B Davis, JJ Tofaris, G Validation of α-synuclein in L1CAM-immunocaptured exosomes as a biomarker for the stratification of Parkinsonian syndromes |
| title | Validation of α-synuclein in L1CAM-immunocaptured exosomes as a biomarker for the stratification of Parkinsonian syndromes |
| title_full | Validation of α-synuclein in L1CAM-immunocaptured exosomes as a biomarker for the stratification of Parkinsonian syndromes |
| title_fullStr | Validation of α-synuclein in L1CAM-immunocaptured exosomes as a biomarker for the stratification of Parkinsonian syndromes |
| title_full_unstemmed | Validation of α-synuclein in L1CAM-immunocaptured exosomes as a biomarker for the stratification of Parkinsonian syndromes |
| title_short | Validation of α-synuclein in L1CAM-immunocaptured exosomes as a biomarker for the stratification of Parkinsonian syndromes |
| title_sort | validation of α synuclein in l1cam immunocaptured exosomes as a biomarker for the stratification of parkinsonian syndromes |
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