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Heterogeneity in α-synuclein fibril activity correlates to disease phenotypes in Lewy body dementia by Arpine Sokratian; Julia Ziaee; Kaela Kelly; Allison Chang; Nicole Bryant; Shijie Wang; Enquan Xu; Joshua Y. Li; Shih-Hsiu Wang; John Ervin; Sandip M. Swain; Rodger A. Liddle; Andrew B. West is a Medicine article available to read on EtoBox.
What is Heterogeneity in α-synuclein fibril activity correlates to disease phenotypes in Lewy body dementia about?
α-Synuclein aggregation underlies pathological changes in Lewy body dementia. Recent studies highlight structural variabilities associated with α-synuclein aggregates in patient populations. Here, we develop a quantitative real-time quaking-induced conversion (qRT-QuIC) assay to measure permissive α-synuclein fibril-templating activity in tissues and cerebrospinal fluid (CSF). The assay is anchored through reference panels of stabilized ultra-short fibril particles. In humanized α-synuclein transgenic mice, qRT-QuIC identifies differential levels of fibril activity across the brain months before the deposition of phosphorylated α-synuclein in susceptible neurons. α-Synuclein fibril activity in cortical brain extracts from dementia with Lewy bodies (DLB) correlates with activity in matched ventricular CSF. Elevated α-synuclein fibril activity in CSF corresponds to reduced survival in DLB. α-Synuclein fibril particles amplified from cases with high fibril activity show superior templating in the formation of new inclusions in neurons relative to the same number of fibril particles amplified from DLB cases with low fibril activity. Our results highlight a previously unknown broad hete
Who reads Heterogeneity in α-synuclein fibril activity correlates to disease phenotypes in Lewy body dementia?
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- Author
- Arpine Sokratian; Julia Ziaee; Kaela Kelly; Allison Chang; Nicole Bryant; Shijie Wang; Enquan Xu; Joshua Y. Li; Shih-Hsiu Wang; John Ervin; Sandip M. Swain; Rodger A. Liddle; Andrew B. West
- Publisher
- Springer Science and Business Media LLC
- Published
- 2021
- Language
- EN
- Field
- Medicine (Life Sciences)