Beyond target engagement: RNA therapeutics and the neuroimmune challenge in tauopathies

Recent advances in RNA-based therapeutics have generated considerable interest as a strategy for targeting tau pathology in Alzheimer's disease and related tauopathies. In their review, Rajbanshi and colleagues provide a comprehensive overview of emerging RNA therapeutic modalities, translational challenges, and ongoing clinical development efforts. This commentary discusses the promise of RNA-based approaches within the broader context of contemporary neurodegeneration research, highlighting the persistent disconnect between molecular target engagement and meaningful clinical benefit. Emerging evidence suggests that successful disease modification may require consideration of neuroimmune dysfunction, biological heterogeneity, and disease stage in addition to molecular pathology. The future success of RNA therapeutics will likely depend not only on achieving precise modulation of tau biology but also on translating these advances into sustained cognitive and functional benefit for patients.