The present study therefore aimed to investigate the therapeutic potential of escitalopram (ESC; SSRI) in combination with galantamine (GAL; AChE inhibitor) on key pathological pathways, including the neurotrophic system, hypothalamic-pituitary-adrenal (HPA) axis, kynurenine pathway, inflammation, and oxidative stress, in an animal model of AD comorbid with depression. The gene discussed is ACHE; the disease is major depressive disorder.