Nature Communications published evidence that TYK2 kinase activity promotes neuroinflammation in Alzheimer’s disease brains with TDP‑43 pathology. The study combined human tissue analysis, mechanistic experiments and pharmacologic inhibition to implicate TYK2 as a mediator of inflammatory signaling linked to neurodegeneration in mixed‑pathology AD cases. Authors showed that TYK2 activation correlated with TDP‑43 burden and inflammatory gene expression signatures. Preclinical models treated with TYK2 inhibitors displayed reductions in inflammatory markers and partial rescue of synaptic and behavioral deficits, supporting translational potential. The paper positions TYK2 as a candidate target for a subset of AD patients characterized by TDP‑43 co-pathology. Because TYK2 inhibitors are already in development for inflammatory diseases, repurposing strategies and biomarker-guided trials are feasible near term. Pharma teams should prioritize biomarker assays for TDP‑43 and TYK2 activation to design targeted proof-of-concept studies. Safety profiles, CNS penetration and patient selection will determine viability for clinical development in neurodegeneration.