ArticleCell2026
Distinct cellular phenotypes of language and executive decline in amyotrophic lateral sclerosis.
Article in Cell, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
3 citing papers in PubMed.
- Uncovering the signatures of aging and senescence in the human dorsolateral prefrontal cortex.Cell genomics · 2026Article
- TDP-43 dysfunction leads to the accumulation of cryptic transposable element-derived exons, crypTEs, in iPSC derived neurons and ALS/FTD patient tissues.bioRxiv : the preprint server for biology · 2026Article
- Integrative analysis reveals generalizable human neurodegenerative disease-associated glial states.bioRxiv : the preprint server for biology · 2025Article
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16 authors.
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Abstract
Cognitive manifestations, including impairments in language and executive functions, are seen in amyotrophic lateral sclerosis (ALS), but the underlying mechanisms remain unclear. We mapped prefrontal cortex regions from ALS patients by integrating spatial and single-nucleus transcriptomics in a cognitively stratified patient cohort. We uncover that cognitive impairment in ALS is associated with distinct patterns of neuronal dysfunction and glial-vascular dysregulation that vary by region and cognitive subtype. Executive dysfunction is linked to reduced mitochondrial and synaptic activity in deep-layer dorsolateral prefrontal cortex neurons, whereas language-related deficits track with a diffuse pan-regional response involving glial and vascular abnormalities. Our analyses, validated by multiplexed imaging, further identify signatures in the prefrontal cortex that span both motor and cognitive phenotypes, including a multicellular gliosis response. The findings reveal that clinical heterogeneity in ALS is driven by phenotype-specific cellular interactions in motor and non-motor regions of the brain.
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