Comparative Evaluation of Imatinib and Nilotinib in a Streptozotocin-Induced Rat Model of Alzheimer's Disease : Neuroprotective, Anti-inflammatory, and Cognitive Outcomes.

OBJECTIVE

Alzheimer's disease is a progressive neurodegenerative disorder characterized by amyloid-beta (Aβ) peptide aggregation, representing a major therapeutic target. Emerging evidence suggests certain chemotherapeutic agents may attenuate Aβ pathology.

METHODS

This study investigated the effects of imatinib, a tyrosine kinase inhibitor with limited blood-brain barrier (BBB) penetration, and nilotinib, with enhanced BBB permeability, in an intracerebroventricular streptozotocin (ICV-STZ) rat model of Alzheimer's disease. Outcomes included behavioral assessments (learning latency), hippocampal CA1 and CA3 neuronal counts, and brain concentrations of tumor necrosis factor (TNF)-α, nuclear factor kappa B (NF-κB), brain-derived neurotrophic factor (BDNF), and neuregulin-1 (NRG-1).

RESULTS

ICV-STZ administration significantly elevated TNF-α and NF-κB levels and reduced BDNF and NRG-1 expression. Both imatinib and nilotinib mitigated these alterations, with imatinib demonstrating greater efficacy despite its limited BBB permeability. Imatinib and nilotinib reduced TNF-α and NF-κB levels, increased BDNF and NRG-1 expression, and significantly improved cognitive performance, with latency periods extending from 69.8 seconds in the disease model to 193.5 and 183.1 seconds, respectively.

CONCLUSION

Imatinib and nilotinib ameliorated neuroinflammation, restored neurotrophic support, and improved cognitive deficits in a preclinical Alzheimer's disease model. These findings highlight the therapeutic potential of tyrosine kinase inhibitors, warranting further translational research in human studies.