Targeting together cholinesterases and serotonin reuptake against Alzheimer’s disease

Abstract Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by cognitive decline and memory loss, with limited therapeutic options. Traditional treatments primarily focus on acetylcholinesterase inhibitors (AChEIs), which aim to increase acetylcholine levels in the brain, and selective serotonin reuptake inhibitors (SSRIs), which modulate serotonin levels. However, these treatments often provide only modest symptom relief. This review explores the potential benefits of combined targeting of cholinesterases and serotonin reuptake as a novel therapeutic strategy for AD. We discuss the pathophysiological role of acetylcholine and serotonin in AD, highlighting their impact on cognitive function, mood regulation, and neuroplasticity. By targeting both cholinergic and serotonergic systems, this dual approach may offer synergistic effects, improving cognitive function, reducing neuropsychiatric symptoms, and enhancing neuroprotective mechanisms. The review also examines preclinical and clinical studies investigating the efficacy of combination therapies and outlines the challenges and opportunities in their development. Ultimately, this combined targeting approach holds promise for providing more effective and comprehensive treatment options for AD, addressing both cognitive and behavioural symptoms associated with the disease.