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Article

RT-QuIC Using C-Terminally Truncated α-Synuclein Forms Detects Differences in Seeding Propensity of Different Brain Regions from Synucleinopathies

1
Neurological Disorder Research Center, Qatar Biomedical Research Institute (QBRI), Hamad Bin Khalifa University (HBKU), Qatar Foundation, Doha 974, Qatar
2
Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne NE2 4AA, UK
3
Core Labs, Qatar Environment and Energy Research Institute (QEERI), Hamad Bin Khalifa University (HBKU), Qatar Foundation, Doha 974, Qatar
4
Newcastle Brain Tissue Resource, Translational and Clinical Research Institute, Campus for Ageing and Vitality, Newcastle University, Newcastle upon Tyne NE4 5PL, UK
*
Author to whom correspondence should be addressed.
Academic Editor: François Ichas
Biomolecules 2021, 11(6), 820; https://doi.org/10.3390/biom11060820
Received: 13 April 2021 / Revised: 22 May 2021 / Accepted: 25 May 2021 / Published: 31 May 2021
Aggregated α-synuclein (αSyn) protein is a core pathological feature of Parkinson’s disease (PD) and dementia with Lewy bodies (DLB). Both PD and DLB demonstrate the presence of diverse intracellular α-synuclein (αSyn) species, including C-terminally truncated αSyn (C-αSyn), although it is unknown how C-αSyn species contribute to disease progression. Using recombinant C-αSyn and PD and DLB brain lysates as seeds in the real-time quaking-induced conversion (RT-QuIC) assay, we explored how C-αSyn may be involved in disease stratification. Comparing the seeding activity of aqueous-soluble fractions to detergent-soluble fractions, and using αSyn 1-130 as substrate for the RT-QuIC assay, the temporal cortex seeds differentiated PD and DLB from healthy controls. In contrast to the temporal cortex, where PD and DLB could not be distinguished, αSyn 1-130 seeded by the detergent-soluble fractions from the PD frontal cortex demonstrated greater seeding efficiency compared to the DLB frontal cortex. Moreover, proteinase K-resistant (PKres) fragments from the RT-QuIC end products using C-αSyn 1-130 or C-αSyn 1-115 were more obvious in the frontal cortex compared to the temporal cortex. Morphological examinations of RT-QuIC end products showed differences in the size of the fibrils between C-αSyn 1-130 and C-αSyn 1-115, in agreement with the RT-QuIC results. These data show that C-αSyn species can distinguish PD from DLB and suggest diversity in αSyn species across these synucleinopathies, which could play a role in disease progression. View Full-Text
Keywords: synucleinopathies; Parkinson’s disease; dementia with Lewy bodies; RT-QuIC; α-synuclein; C-terminally truncated αSyn synucleinopathies; Parkinson’s disease; dementia with Lewy bodies; RT-QuIC; α-synuclein; C-terminally truncated αSyn
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MDPI and ACS Style

Poggiolini, I.; Erskine, D.; Vaikath, N.N.; Ponraj, J.; Mansour, S.; Morris, C.M.; El-Agnaf, O.M.A. RT-QuIC Using C-Terminally Truncated α-Synuclein Forms Detects Differences in Seeding Propensity of Different Brain Regions from Synucleinopathies. Biomolecules 2021, 11, 820. https://doi.org/10.3390/biom11060820

AMA Style

Poggiolini I, Erskine D, Vaikath NN, Ponraj J, Mansour S, Morris CM, El-Agnaf OMA. RT-QuIC Using C-Terminally Truncated α-Synuclein Forms Detects Differences in Seeding Propensity of Different Brain Regions from Synucleinopathies. Biomolecules. 2021; 11(6):820. https://doi.org/10.3390/biom11060820

Chicago/Turabian Style

Poggiolini, Ilaria, Daniel Erskine, Nishant N. Vaikath, Janarthanan Ponraj, Said Mansour, Christopher M. Morris, and Omar M.A. El-Agnaf 2021. "RT-QuIC Using C-Terminally Truncated α-Synuclein Forms Detects Differences in Seeding Propensity of Different Brain Regions from Synucleinopathies" Biomolecules 11, no. 6: 820. https://doi.org/10.3390/biom11060820

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