Tauopathies are a class of neurodegenerative disorders in which tau protein accumulates abnormally in the brain and contributes to progressive neurodegeneration. Given the central role of abnormal tau accumulation in tauopathy progression, targeted protein degradation (TPD) has emerged as a promising therapeutic platform for selectively eliminating pathogenic proteins, expanding therapeutic opportunities beyond conventional small-molecule inhibitors. Among these approaches, autophagosome-tethering chimeras (ATTECs) are bifunctional molecules that bind both LC3 and a target protein, thereby inducing autophagic degradation. In this study, we found that Tau-ATTECs selectively degraded tau, reduced p-tau, and exerted neuroprotective effects in cell-based models. We also identified an orally available Tau-ATTEC that penetrated the blood-brain barrier and reduced pathological tau levels in a P301S transgenic model. Optimized Tau-ATTEC derivatives showed the degradation of truncated tau or p-tau in cell based model. Based on these findings, further Tau-ATTEC derivatives are being synthesized and optimized, and their efficacy will be evaluated in cell-based models, followed by in vivo studies to assess blood-brain barrier penetration. Supported by the therapeutic potential observed in P301S transgenic model, further optimization may lead to the identification of more effective Tau-ATTECs and ultimately to the selection of a preclinical candidate.