Serotonergic Modulators in Alzheimer's Disease: A Hope in the Hopeless Condition

Alzheimer's disease (AD) is the main cause of dementia worldwide. AD is a progressive brain neurodegenerative disease due to genetic and environmental factors that induce a progressive accumulation of intracellular hyperphosphorylated tau protein and extracellular amyloid protein (Aβ). However, anti-AD medications cannot reverse the fundamental AD neuropathology due to amyloid plaques and related oxidative stress and inflammatory reactions. Thus, targeting other pathways might be reasonable in the management of AD. The serotonin (5-HT) neurotransmitter plays a crucial role in preventing neurodegeneration and related oxidative stress and inflammatory reactions. In addition, the serotonergic system is highly dysregulated in many neurodegenerative diseases, including AD. Deregulation of serotonin synthesis and its receptors is involved in the pathogenesis of AD. Therefore, this review aims to discuss how the serotonergic system is affected in AD, and how 5-HT modulators can reverse AD neuropathology and alleviate the associated neuropsychiatric disorders in AD patients.