Background Alzheimer’s disease (AD) is an incurable neurodegenerative disorder and a major cause of dementia. Some of the hallmarks of AD include presence of amyloid plaques in brain parenchyma, calcium dysregulation within individual neurons, and neuroinflammation. A promising therapeutic would reverse or stymie these pathophysiologies in an animal model of AD.
Methods We tested the effect of NB-02, previously known as DA-9803, a novel multimodal therapeutic, on amyloid deposition, neuronal calcium regulation and neuroinflammation in 8-10 month old APP mice, an animal model of AD.
Results In vivo multiphoton microscopy revealed that 2 month-long administration of NB-02 halted amyloid plaque deposition and cleared amyloid in the cortex. Post-mortem analysis verified NB-02-dependent decrease in plaque deposition in the cortex as well as hippocampus. Furthermore, drug treatment reversed neuronal calcium elevations, thus restoring neuronal function. Finally, NB-02 transformed the morphology of astrocytes and microglia to a more phagocytic state, affecting neuroinflammation.
Conclusions NB-02 was effective at reversing AD neuropathophysiology in an animal model. Therefore, in addition to serving as a promising preventative agent, NB-02 holds potential as a treatment for AD in the clinic.