Since the discovery of TAR DNA-binding protein 43 (TDP-43) in 1995, our understanding of its role continues to expand as research progresses. In particular, its role in the pathogenesis of Alzheimer's disease (AD) has drawn increasing interest in recent years. TDP-43 may participate in various pathogenic mechanisms underlying AD, such as amyloid β deposition, tau hyperphosphorylation, mitochondrial dysfunction, and neuroinflammation. Because AD is complex and heterogeneous, and because of the distinct characteristics of TDP-43, mostly seen in the oldest-old and those with more severe clinical phenotype, subcategorization based on specific features or biomarkers may significantly improve diagnosis and treatment. AD-like cognitive dysfunction associated with TDP-43 pathology may therefore be a distinct encephalopathy, referred to as limbic-predominant age-related TDP-43 encephalopathy (LATE).

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Objectives To verify whether mesenchymal stem cells cocultured with tanshinone IIA may ameliorate Alzheimer's disease by inhibiting oxidative stress.Methods Sixty male Sprague-Dawley rats were randomly divided into 4 groups named Sham, Aβ 25-35 , mesenchymal stem cells, and mesenchymal stem cells (tanshinone IIA). The rats were treated according to different groups. The neurobehavioral performance of Sprague-Dawley rats was evaluated via Morris water maze test. Histological changes were checked via hematoxylin-eosin staining. The levels of total antioxidant activity (T-AOC), superoxide dismutase (SOD), glutathione peroxidase (GSH-PX) and malondialdehyde in hippocampus were assayed by ELISA kit. The levels of Aβ, p-tau/tau, and p-AMP-activated protein kinase/AMPactivated protein kinase in hippocampus were checked by Western blot. ResultsOur research showed that the injection of mesenchymal stem cells (tanshinone IIA) into the hippocampus alleviated learning and memory deficits and reduced hippocampal neuronal injury in the Alzheimer's disease rats. Moreover, mesenchymal stem cells (tanshinone IIA) treatment suppressed oxidative stress, attenuated Aβ accumulation reduced Tau hyperphosphorylation, and enhanced the activity of AMP-activated protein kinase in the hippocampus of the Alzheimer's disease rats. However, there were almost no significant difference between the mesenchymal stem cells and Aβ 25-35 groups.Conclusions Mesenchymal stem cells (tanshinone IIA) transplantation may be a potential treatment for curing Alzheimer's disease, which may be related to the inhibition of oxidative stress.