A novel approach to evaluate alpha-synuclein seeding shows a wide heterogeneity in multiple system atrophy
Abstract Severalin vitroandin vivofindings have consistently shown that α-synuclein derived from multiple system atrophy (MSA) subjects has more seeding capacity than Parkinson’s disease-derived α-synuclein. However, reliable detection of α-synuclein derived from MSA using seeded amplification assays, such as the Real-Time Quaking-induced Conversion, has remained challenging. Here we demonstrate that the interaction of the Thioflavin T dye with α-synuclein from MSA and Parkinson’s disease patients can be modulated by the type of salt, pH, and ionic strength used to generate strain-specific reaction buffers. Employing this novel approach, we have generated a streamlined Real-Time Quaking-induced Conversion assay capable of categorizing MSA brains according to their α-synuclein seeding behavior, and to unravel a previously unrecognized heterogeneity in seeding activity between different brain regions of a given individual that goes beyond immunohistochemical observations and provide a framework for future molecular subtyping of MSA..
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Preprint| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
bioRxiv.org - (2023) vom: 07. Jan. Zur Gesamtaufnahme - year:2023 |
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| Sprache: |
Englisch |
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| Beteiligte Personen: |
Martinez-Valbuena, Ivan [VerfasserIn] |
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| doi: |
10.1101/2021.08.10.455800 |
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| PPN (Katalog-ID): |
XBI032373023 |
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| 245 | 1 | 0 | |a A novel approach to evaluate alpha-synuclein seeding shows a wide heterogeneity in multiple system atrophy |
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| 520 | |a Abstract Severalin vitroandin vivofindings have consistently shown that α-synuclein derived from multiple system atrophy (MSA) subjects has more seeding capacity than Parkinson’s disease-derived α-synuclein. However, reliable detection of α-synuclein derived from MSA using seeded amplification assays, such as the Real-Time Quaking-induced Conversion, has remained challenging. Here we demonstrate that the interaction of the Thioflavin T dye with α-synuclein from MSA and Parkinson’s disease patients can be modulated by the type of salt, pH, and ionic strength used to generate strain-specific reaction buffers. Employing this novel approach, we have generated a streamlined Real-Time Quaking-induced Conversion assay capable of categorizing MSA brains according to their α-synuclein seeding behavior, and to unravel a previously unrecognized heterogeneity in seeding activity between different brain regions of a given individual that goes beyond immunohistochemical observations and provide a framework for future molecular subtyping of MSA. | ||
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| 700 | 1 | |a Visanji, Naomi P. |e verfasserin |4 aut | |
| 700 | 1 | |a Kim, Ain |e verfasserin |4 aut | |
| 700 | 1 | |a Lau, Heather H. C. |e verfasserin |4 aut | |
| 700 | 1 | |a So, Raphaella W. L. |e verfasserin |4 aut | |
| 700 | 1 | |a Alshimemeri, Sohaila |e verfasserin |4 aut | |
| 700 | 1 | |a Gao, Andrew |e verfasserin |4 aut | |
| 700 | 1 | |a Seidman, Michael |e verfasserin |4 aut | |
| 700 | 1 | |a Luquin, Maria R. |e verfasserin |4 aut | |
| 700 | 1 | |a Watts, Joel C. |e verfasserin |4 aut | |
| 700 | 1 | |a Lang, Anthony E. |e verfasserin |4 aut | |
| 700 | 1 | |a Kovacs, Gabor G. |e verfasserin |4 aut | |
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