α-Synuclein aggregates amplified from patient-derived Lewy bodies recapitulate Lewy body diseases in mice

Norihito Uemura (), Nicholas P. Marotta, Jahan Ara, Emily S. Meymand, Bin Zhang, Hiroshi Kameda, Masato Koike, Kelvin C. Luk, John Q. Trojanowski and Virginia M.-Y. Lee ()
Additional contact information
Norihito Uemura: University of Pennsylvania School of Medicine
Nicholas P. Marotta: University of Pennsylvania School of Medicine
Jahan Ara: University of Pennsylvania School of Medicine
Emily S. Meymand: University of Pennsylvania School of Medicine
Bin Zhang: University of Pennsylvania School of Medicine
Hiroshi Kameda: Juntendo University Graduate School of Medicine
Masato Koike: Juntendo University Graduate School of Medicine
Kelvin C. Luk: University of Pennsylvania School of Medicine
John Q. Trojanowski: University of Pennsylvania School of Medicine
Virginia M.-Y. Lee: University of Pennsylvania School of Medicine

Nature Communications, 2023, vol. 14, issue 1, 1-17

Abstract: Abstract Extraction of α-Synuclein (αSyn) aggregates from Lewy body disease (LBD) brains has been widely described yet templated fibrillization of LB-αSyn often fails to propagate its structural and functional properties. We recently demonstrated that aggregates amplified from LB-αSyn (ampLB) show distinct biological activities in vitro compared to human αSyn preformed fibrils (hPFF) formed de novo. Here we compare the in vivo biological activities of hPFF and ampLB regarding seeding activity, latency in inducing pathology, distribution of pathology, inclusion morphology, and cell-type preference. Injection of ampLB into mice expressing only human αSyn (male Thy1:SNCA/Snca–/– mice) induced pathologies similar to those of LBD subjects that were distinct from those induced by hPFF-injection or developing spontaneously with aging. Importantly, αSyn aggregates in ampLB-injected Thy1:SNCA/Snca–/– mice maintained the unique biological and conformational features of original LB-αSyn. These results indicate that ampLB-injection, rather than conventional PFF-injection or αSyn overexpression, faithfully models key aspects of LBD.

Date: 2023
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-023-42705-5 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-42705-5

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-023-42705-5

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().