Imaging spatial transcriptomics reveals molecular patterns of vulnerability to pathology in a transgenic α-synucleinopathy model.

ABSTRACT: In Parkinson's disease and dementia with Lewy bodies, aggregated and phosphorylated α-synuclein pathology appears in select neurons throughout cortical and subcortical regions, but little is currently known about why certain populations are selectively vulnerable. Here, using imaging spatial transcriptomics (IST) coupled with downstream immunofluorescence for α-synuclein phosphorylated at Ser129 (pSyn) in the same tissue sections, we identified neuronal subtypes in the cortex and hippocampus of transgenic human α-synuclein-overexpressing mice that preferentially developed pSyn pathology. Additionally, we investigated the transcriptional underpinnings of this vulnerability, pointing to expression of Plk2, which phosphorylates α-synuclein at Ser129, and human SNCA (hSNCA

SUBMITTER: Horan-Portelance L 

PROVIDER: S-EPMC11451628 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature