Cell | 渐冻症语言与执行功能衰退的差异细胞基础

TL;DR - A Cell study combining spatial transcriptomics and single-nucleus RNA sequencing identifies distinct cellular mechanisms behind language and executive-function decline in ALS. The findings clarify ALS cognitive heterogeneity and suggest phenotype-specific therapeutic targets.

• Language impairment correlated with diffuse glial–vascular dysregulation in the BA44/45 language region, including altered perivascular myeloid-cell activity.
• Executive dysfunction was linked to reduced mitochondrial, oxidative-phosphorylation, and synaptic activity in deep-layer BA46 excitatory and inhibitory neurons.
• Reactive astrocytes, microglia, and stressed oligodendrocyte precursor cells increased across ALS samples, indicating a coordinated gliosis response.
• Gliosis occurred independently of TDP-43 pathology, while oligodendrocyte-lineage abundance tracked neuronal synaptic and mitochondrial dysregulation.