α-Synuclein seeding activity in duodenum biopsies from Parkinson's disease patients.
Abnormal deposition of α-synuclein is a key feature and biomarker of Parkinson's disease. α-Synuclein aggregates can propagate themselves by a prion-like seeding-based mechanism within and between tissues and are hypothesized to move between the intestine and brain. α-Synuclein RT-QuIC seed amp...
| Main Authors: | , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2023-06-01
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| Series: | PLoS Pathogens |
| Online Access: | https://doi.org/10.1371/journal.ppat.1011456 |
| _version_ | 1797786534256050176 |
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| author | Sarah Vascellari Christina D Orrù Bradley R Groveman Sabiha Parveen Giuseppe Fenu Giada Pisano Giuseppe Piga Giulia Serra Valentina Oppo Daniela Murgia Andrea Perra Fabrizio Angius Andrew G Hughson Cathryn L Haigh Aldo Manzin Giovanni Cossu Byron Caughey |
| author_facet | Sarah Vascellari Christina D Orrù Bradley R Groveman Sabiha Parveen Giuseppe Fenu Giada Pisano Giuseppe Piga Giulia Serra Valentina Oppo Daniela Murgia Andrea Perra Fabrizio Angius Andrew G Hughson Cathryn L Haigh Aldo Manzin Giovanni Cossu Byron Caughey |
| author_sort | Sarah Vascellari |
| collection | DOAJ |
| description | Abnormal deposition of α-synuclein is a key feature and biomarker of Parkinson's disease. α-Synuclein aggregates can propagate themselves by a prion-like seeding-based mechanism within and between tissues and are hypothesized to move between the intestine and brain. α-Synuclein RT-QuIC seed amplification assays have detected Parkinson's-associated α-synuclein in multiple biospecimens including post-mortem colon samples. Here we show intra vitam detection of seeds in duodenum biopsies from 22/23 Parkinson's patients, but not in 6 healthy controls by RT-QuICR. In contrast, no tau seeding activity was detected in any of the biopsies. Our seed amplifications provide evidence that the upper intestine contains a form(s) of α-synuclein with self-propagating activity. The diagnostic sensitivity and specificity for PD in this biopsy panel were 95.7% and 100% respectively. End-point dilution analysis indicated up to 106 SD50 seeding units per mg of tissue with positivity in two contemporaneous biopsies from individual patients suggesting widespread distribution within the superior and descending parts of duodenum. Our detection of α-synuclein seeding activity in duodenum biopsies of Parkinson's disease patients suggests not only that such analyses may be useful in ante-mortem diagnosis, but also that the duodenum may be a source or a destination for pathological, self-propagating α-synuclein assemblies. |
| first_indexed | 2024-03-13T01:09:18Z |
| format | Article |
| id | doaj.art-f1359ada37b94233a8723855297fbd28 |
| institution | Directory Open Access Journal |
| issn | 1553-7366 1553-7374 |
| language | English |
| last_indexed | 2024-03-13T01:09:18Z |
| publishDate | 2023-06-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Pathogens |
| spelling | doaj.art-f1359ada37b94233a8723855297fbd282023-07-06T05:30:56ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742023-06-01196e101145610.1371/journal.ppat.1011456α-Synuclein seeding activity in duodenum biopsies from Parkinson's disease patients.Sarah VascellariChristina D OrrùBradley R GrovemanSabiha ParveenGiuseppe FenuGiada PisanoGiuseppe PigaGiulia SerraValentina OppoDaniela MurgiaAndrea PerraFabrizio AngiusAndrew G HughsonCathryn L HaighAldo ManzinGiovanni CossuByron CaugheyAbnormal deposition of α-synuclein is a key feature and biomarker of Parkinson's disease. α-Synuclein aggregates can propagate themselves by a prion-like seeding-based mechanism within and between tissues and are hypothesized to move between the intestine and brain. α-Synuclein RT-QuIC seed amplification assays have detected Parkinson's-associated α-synuclein in multiple biospecimens including post-mortem colon samples. Here we show intra vitam detection of seeds in duodenum biopsies from 22/23 Parkinson's patients, but not in 6 healthy controls by RT-QuICR. In contrast, no tau seeding activity was detected in any of the biopsies. Our seed amplifications provide evidence that the upper intestine contains a form(s) of α-synuclein with self-propagating activity. The diagnostic sensitivity and specificity for PD in this biopsy panel were 95.7% and 100% respectively. End-point dilution analysis indicated up to 106 SD50 seeding units per mg of tissue with positivity in two contemporaneous biopsies from individual patients suggesting widespread distribution within the superior and descending parts of duodenum. Our detection of α-synuclein seeding activity in duodenum biopsies of Parkinson's disease patients suggests not only that such analyses may be useful in ante-mortem diagnosis, but also that the duodenum may be a source or a destination for pathological, self-propagating α-synuclein assemblies.https://doi.org/10.1371/journal.ppat.1011456 |
| spellingShingle | Sarah Vascellari Christina D Orrù Bradley R Groveman Sabiha Parveen Giuseppe Fenu Giada Pisano Giuseppe Piga Giulia Serra Valentina Oppo Daniela Murgia Andrea Perra Fabrizio Angius Andrew G Hughson Cathryn L Haigh Aldo Manzin Giovanni Cossu Byron Caughey α-Synuclein seeding activity in duodenum biopsies from Parkinson's disease patients. PLoS Pathogens |
| title | α-Synuclein seeding activity in duodenum biopsies from Parkinson's disease patients. |
| title_full | α-Synuclein seeding activity in duodenum biopsies from Parkinson's disease patients. |
| title_fullStr | α-Synuclein seeding activity in duodenum biopsies from Parkinson's disease patients. |
| title_full_unstemmed | α-Synuclein seeding activity in duodenum biopsies from Parkinson's disease patients. |
| title_short | α-Synuclein seeding activity in duodenum biopsies from Parkinson's disease patients. |
| title_sort | α synuclein seeding activity in duodenum biopsies from parkinson s disease patients |
| url | https://doi.org/10.1371/journal.ppat.1011456 |
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