RT Journal Article
SR Electronic
T1 A novel approach to evaluate alpha-synuclein seeding shows a wide heterogeneity in multiple system atrophy
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2021.08.10.455800
DO 10.1101/2021.08.10.455800
A1 Ivan Martinez-Valbuena
A1 Naomi P. Visanji
A1 Ain Kim
A1 Heather H. C. Lau
A1 Raphaella W. L. So
A1 Sohaila Alshimemeri
A1 Andrew Gao
A1 Michael Seidman
A1 Maria R. Luquin
A1 Joel C. Watts
A1 Anthony E. Lang
A1 Gabor G. Kovacs
YR 2021
UL http://biorxiv.org/content/early/2021/08/10/2021.08.10.455800.abstract
AB Several in vitro and in vivo findings 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.Competing Interest StatementGGK holds shared patent for the 5G4 antibody. Other authors declare no competing interests.