Cognitive dysfunction is a common clinically neurological disease, especially with a high incidences in the elderly patients. Abnormal expression of Tau protein can cause the occurrence of cognitive dysfunction and is often associated with the severity of illness. This article overviews the relationship between Tau protein and cognitive dysfunction as well as mechanisms and clinical applications of Tau protein leading to cognitive dysfunction. We reviewed research advances on a variety of post-translational modifications of Tau， propagation mechanisms of Tau protein, neurological protection strategies targeting at Tau protein and Tau positron emission computed tomography (PET) imaging technology. The mechanisms of Tau protein leading to cognitive dysfunction can provide new implications on diagnosis and treatment of cognitive dysfunction.