한빛사논문
- 조회314
Ehsan Dadgar-Kiani1,2,8, Gregor Bieri3,8, Ronald Melki4, Aaron D. Gitler3,7, Jin Hyung Lee1,2,5,6,9
1Department of Neurology and Neurological Sciences, Stanford University, Stanford, CA 94305, USA
2Department of Bioengineering, Stanford University, Stanford, CA 94305, USA
3Department of Genetics, Stanford University, Stanford, CA 94305, USA
4Institut François Jacob, MIRCen, CEA and Laboratory of Neurodegenerative Diseases, CNRS, 92265 Fontenay-Aux-Roses, France
5Department of Electrical Engineering, Stanford University, Stanford, CA 94305, USA
6Department of Neurosurgery, Stanford University, Stanford, CA 94305, USA
7Chan Zuckerberg Biohub, San Francisco, CA 94158, USA
Corresponding authors: Aaron D. Gitler, Jin Hyung Lee
Abstract
An emerging view regarding neurodegenerative diseases is that discreet seeding of misfolded proteins leads to widespread pathology. However, the mechanisms by which misfolded proteins seed distinct brain regions and cause differential whole-brain pathology remain elusive. We used whole-brain tissue clearing and high-resolution imaging to longitudinally map pathology in an α-synuclein pre-formed fibril injection model of Parkinson's disease. Cleared brains at different time points of disease progression were quantitatively segmented and registered to a standardized atlas, revealing distinct phases of spreading and decline. We then fit a computational model with parameters that represent α-synuclein pathology spreading, aggregation, decay, and gene expression pattern to this longitudinal dataset. Remarkably, our model can generalize to predicting α-synuclein spreading patterns from several distinct brain regions and can even estimate their origins. This model empowers mechanistic understanding and accurate prediction of disease progression, paving the way for the development and testing of therapeutic interventions.
논문정보
- Research article
- 2022년 11월 (BRIC 등록일 2023-01-13)
- 국외 연구진
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