DNA damage drives a unique, Alzheimer’s disease-relevant senescent state in neurons

DNA damage in patient-derived neurons drives a senescent-like neuronal state relevant to Alzheimer's disease.

• DNA damage induces a senescent-like state in neurons that aligns with features observed in Alzheimer's disease.
• Senescent neurons exhibit significant transcriptional similarities with neurons from Alzheimer's patients.
• A network analysis identifies candidate regulators linked to the senescent-like state in neurons.
• Neurons and fibroblasts display distinct senescence signatures following DNA damage, with neurons showing a p21-associated phenotype.
• Neurons develop a senescence-associated secretory phenotype (SASP) and exhibit predicted activation of NF-κκ1, unlike fibroblasts.
• Neurons also demonstrate a higher accumulation of DNA damage lesions compared to fibroblasts during early responses to DNA damage.

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