The Highly Selective 5-HT2B Receptor Antagonist MW073 Mitigates Aggressive Behavior in an Alzheimer’s Disease Mouse Model

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1. ABSTRACT Alzheimer’s disease (AD) is a multifactorial neurodegenerative disorder and the leading cause of dementia worldwide. Progressive synaptic and neuronal loss underlies the decline in cognition and daily functioning, often accompanied by behavioral and psychological symptoms. Among these, neuropsychiatric disturbances such as agitation and aggression affect 20–65% of patients and represent a major source of caregiver burden. The serotonin receptor antagonist MW073 has recently emerged as a potential therapeutic candidate, showing efficacy in counteracting Aβ- and tau-induced synaptic and memory deficits in AD mouse models. Here, we investigated whether MW073 also mitigates aggressive behavior in Tg2576 mice, a widely used AD model that also displays heightened aggressiveness. Our findings demonstrate that MW073 significantly reduced aggressive tendencies in Tg2576 mice, suggesting that serotonergic modulation may represent a promising strategy to address both cognitive and neuropsychiatric symptoms of AD.

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