Alzheimers disease(AD)is one of the most common neurodegenerative diseases.It is characterized by two histopathological hallmarks,extracellular deposits of β-amyloid and intracellular neurofibrillary tangles(NFTs)[1].The latter are composed of the abnormal aggregation of tau protein [2],of which the normal form plays an important role in stabilizing the microtubules.Recent studies demonstrate that Aβ requires tau protein to induce the cytotoxicity,and the reduction of tau protein protects neurons against Aβ-induced various defects [3].However,tau protein is non-enzymatic and has no compact ligand binding pockets.It is of great challenge to make the diseases-associated non-enzymatic protein susceptible to small molecules control equally.Herein,we design and synthesize a series of peptides that can target tau protein and degrade it controllably.