Therapeutic Potential of a Gadolinium Chelate Complex Conjugated with Vanillic Acid for Alzheimer's Disease

Magnetic resonance imaging (MRI) is a widely used diagnostic tool for neurodegenerative diseases, including Alzheimer's disease. A gadolinium chelate conjugated with vanillic acid (Gd-DO3A-Va) serves as a contrast agent that specifically targets activated microglia in the brains of Alzheimer's disease animal models, such as the 5XFAD mouse. In this study, we evaluated the therapeutic potential of Gd-DO3A-Va in this model. The 5XFAD mouse exhibits neuroinflammation, characterized by activation of the c-Jun N-terminal kinase signaling pathway, inflammasome activation, and increased amyloid-β (Aβ) productionall of which are pathological features of Alzheimer's disease. Treatment with Gd-DO3A-Va reduced inflammatory responses and Aβ deposits. Additionally, the peri-plaque dendritic loss observed in the brains of 5XFAD mice was attenuated following Gd-DO3A-Va treatment. Moreover, Gd-DO3A-Va treatment prevented memory loss, as indicated by the Y-maze test. Taken together, these findings suggest that Gd-DO3A-Va, an MR contrast agent that provides disease-specific signal enhancement in the brains of animal models of Alzheimer's disease, shows promising therapeutic potential for preventing disease progression by suppressing inflammation and inhibiting Aβ production. Therefore, Gd-DO3A-Va could serve as a theranostic agent for Alzheimer's disease.