Homocysteine‐Driven Disruption of Neurotrophic and Inflammatory Circuits in the Hippocampus: Novel Insights into Alzheimer's Therapeutics with Rivastigmine and Ibuprofen

HHcy disrupts hippocampal neurotrophic and inflammatory circuits and alters DNA methylation profiles relevant to AD pathology. Rivastigmine treatment reversed alterations in TrkB and VEGF levels, IL-1β expression, and global DNA methylation, while Ibuprofen reduced CCL5/RANTES content, showing distinct neuroprotective effects through modulation of neurotrophic and inflammatory pathways. These findings highlight the potential of pharmacological strategies targeting key molecular features of AD. Importantly, they reinforce the utility of HHcy as a translational model for AD, providing insight into key processes such as impaired neurotrophic signaling, chronic neuroinflammation, and epigenetic dysregulation - hallmarks of the disease and promising therapeutic targets.