The important role of TDP-43 proteinopathy in Alzheimer's disease (AD) has been gradually revealed. High proportion of AD patients have TDP-43 proteinopathy on their postmortem diagnosis. Patients with TDP-43 proteinopathy show more sever hippocampal atrophy and cognitive dysfunction, suggesting that TDP-43 proteinopathy can serve as an important target in AD diagnosis and treatment. Evaluation of TDP-43 proteinopathy in vivo would hold great promise in AD diagnosis, drug development and treatment. In this review, we describe the pathological characteristics of TDP-43 proteinopathy in AD, and summarize the recent progress of TDP-43 proteinopathy in the diagnosis and treatment of AD.