Objective To study the expression change of sFRP4 in the spinal cord of adult amyotrophic lateral sclerosis(ALS) transgenic mice, and explore the role of sFRP4 in the pathogenesis of ALS. Methods Both the ALS transgenic mice and wild-type mice were selected, some were perfused intracardially with 4% paraformaldehyde at the age of 95days, 108days and 122days.Their spinal cords were dissected and sectioned. Some mice were anesthetized and spinal cords were quickly removed. RNA and total protein were obtained. The distribution of sFRP4 positive cells, and expression changes of sFRP4 mRNA and protein in the spinal cord of adult ALS transgenic mice and wild-type mice were observed by immunohistochemical techniques, RT-PCR and Western blotting at different time points. Results Compared with wild-type mice, sFRP4 mRNA and protein expression were all increased significantly in the spinal cord of ALS transgenic mice at the age of 95days, 108days, and 122days(EM>P /EM>< 0.05).The majority of sFRP4 positive cells were located in the ventral horn of the gray matter. Nerve fibers were also positive within the white matter. Compared with wild-type mice, sFRP4 positive cells were increased distinctly. sFRP4-labeled cells were co-expressed GFAP and β-tubulinIII in the ALS transgenic mice and wild-type mice, and sFRP4/GFAP double positive cells were increased in ALS transgenic mice.Conclusion BR>sFRP4 positive cells were increased significantly, and the expression of sFRP4 mRNA and protein were increased in the spinal cord of ALS transgenic mice, suggesting that sFRP4 may be closely related to the pathogenesis of amyotrophic latera