Mesoscale connections and gene expression empower whole-brain modeling of α-synuclein spread, aggregation, and decay dynamics.

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 dat

SUBMITTER: Dadgar-Kiani E 

PROVIDER: S-EPMC10840492 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature