Lack of a key gene in brain immune cells creates aging-like changes and social memory problems in mice linked to ALS and FTD

Deleting Tbk1 from microglia leads to a pro-inflammatory signature associated with early social recognition deficits.

• Loss of Tbk1 in mouse motor neurons does not trigger transcriptional stress, despite signs of autophagy deregulation.
• Tbk1 deletion in microglia results in altered homeostasis and reactive responses.
• In both the spinal cord and brain, Tbk1 deletion promotes a microglial profile indicative of ageing and neurodegeneration.
• Microglial Tbk1 deletion does not cause ALS-like motor neuron damage but is sufficient to induce early FTD-like social recognition deficits.
• The observed social recognition deficits are linked to microglial activation and T cell infiltration in specific brain regions.

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