A fusion protein used for preventing and treating Alzheimer's disease, a preparation method therefor, and an application thereof. The fusion protein comprises the extracellular domain of human p75NTR human IL-33 and a linker peptide respectively connected to the carboxyl terminus of the p75NTR-ECD and the amino terminus of the human IL-33. The amino acid sequence of the p75NTR-ECD is as shown in SEQ ID NO: 1, and the nucleotide sequence is as shown in SEQ ID NO: 2. The amino acid sequence of the human IL-33 is as shown in SEQ ID NO: 3, and the nucleotide sequence is as shown in SEQ ID NO. 4. The invention overcomes the defects of the p75NTR-ECD or a fusion protein p75NTR-ECD-FC), for preventing and treating Alzheimer's disease. In addition, the functions of the IL-33 and the p75NTR-ECD are combined together, and the biological activity for preventing and treating Alzheimer's disease is significantly increased.