期刊
BIOMOLECULES
卷 11, 期 6, 页码 -出版社
MDPI
DOI: 10.3390/biom11060820
关键词
synucleinopathies; Parkinson's disease; dementia with Lewy bodies; RT-QuIC; alpha-synuclein; C-terminally truncated alpha Syn
资金
- Lundbeck A/S [13737]
- Qatar Biomedical Research Institute [SF 2017-0007]
The study revealed that C-alpha Syn species can distinguish between PD and DLB, suggesting that the diversity of alpha Syn species in these synucleinopathies may play a role in disease progression.
Aggregated alpha-synuclein (alpha Syn) 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 alpha-synuclein (alpha Syn) species, including C-terminally truncated alpha Syn (C-alpha Syn), although it is unknown how C-alpha Syn species contribute to disease progression. Using recombinant C-alpha Syn and PD and DLB brain lysates as seeds in the real-time quaking-induced conversion (RT-QuIC) assay, we explored how C-alpha Syn may be involved in disease stratification. Comparing the seeding activity of aqueous-soluble fractions to detergent-soluble fractions, and using alpha Syn 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, alpha Syn 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-alpha Syn 1-130 or C-alpha Syn 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-alpha Syn 1-130 and C-alpha Syn 1-115, in agreement with the RT-QuIC results. These data show that C-alpha Syn species can distinguish PD from DLB and suggest diversity in alpha Syn species across these synucleinopathies, which could play a role in disease progression.
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