Differential Cellular Mechanisms Underlie Language and Executive Decline in Amyotrophic Lateral Sclerosis.

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Tác giả: Obadele Casel, Aidan Daly, Jacqueline Eschbach, Jenna M Gregory, Christopher A Jackson, Kristy Kang, Matthew Leung, Karina McDade, Joana Petrescu, Hemali Phatnani, Luke Reilly, Cláudio Gouveia Roque, Colin Smith

Ngôn ngữ: eng

Ký hiệu phân loại:

Thông tin xuất bản: United States : bioRxiv : the preprint server for biology , 2025

Mô tả vật lý:

Bộ sưu tập: NCBI

ID: 683661

Half of all amyotrophic lateral sclerosis (ALS) patients demonstrate a spectrum of cognitive and behavioral changes over the course of the disease, but the mechanisms underlying this heterogeneity remain unclear. We assemble a high-resolution cellular map of prefrontal cortex regions of the ALS brain by integrating spatial and single-nucleus transcriptomic profiles of a cognitively stratified ALS patient cohort that includes non-neuropathological controls. We find cellular programs characteristic of ALS, including a frequent gliotic response. We also find that executive and language cognitive impairments differ from ALS without cognitive impairment, and from each other, in the extent and pattern of neuronal dysregulation and neuron-glial interactions across different brain regions. These findings reveal a relationship between cognitive phenotype and prefrontal cortex dysfunction in ALS.
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