Single-cell transcriptomic and neuropathologic analysis reveals dysregulation of the integrated stress response in progressive supranuclear palsy.

ABSTRACT: Progressive supranuclear palsy (PSP) is a sporadic neurodegenerative tauopathy variably affecting brainstem and cortical structures, and characterized by tau inclusions in neurons and glia. The precise mechanism whereby these protein aggregates lead to cell death remains unclear. To investigate the contribution of these different cellular abnormalities to PSP pathogenesis, we performed single-nucleus RNA sequencing (snRNA-seq) and analyzed 50,708 high quality nuclei targeting the diencephalon, including the subthalamic nucleus and adjacent structures, from human post-mortem PSP brains with varying degrees of pathology compared to controls. Cell-type-specific differential expression and pathway analysis identified both common and discrete changes in numerous pathways previously implicated i

SUBMITTER: Whitney K 

PROVIDER: S-EPMC11625691 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature