The chapter discusses the neurotoxic effects of amyloid β-protein (Aβ) and its impact on synaptic and network dysfunction in Alzheimer's disease (AD). It highlights the complexity of Aβ's effects, which involve various soluble and insoluble forms of the peptide, including monomers, oligomers, and fibrils. The authors emphasize that Aβ can induce synaptic dysfunction and network disorganization through multiple mechanisms, such as binding to different cellular components and affecting various signaling pathways. The chapter also reviews the role of Aβ in modulating synaptic transmission, both positively and negatively, and the potential therapeutic implications of targeting these processes. Additionally, it explores the possibility that Aβ-induced synaptic and network alterations may contribute significantly to the cognitive and behavioral deficits observed in AD patients. The authors suggest that therapeutic strategies should focus on reducing Aβ levels and enhancing the brain's resistance to Aβ by targeting copathogenic factors or downstream mechanisms.The chapter discusses the neurotoxic effects of amyloid β-protein (Aβ) and its impact on synaptic and network dysfunction in Alzheimer's disease (AD). It highlights the complexity of Aβ's effects, which involve various soluble and insoluble forms of the peptide, including monomers, oligomers, and fibrils. The authors emphasize that Aβ can induce synaptic dysfunction and network disorganization through multiple mechanisms, such as binding to different cellular components and affecting various signaling pathways. The chapter also reviews the role of Aβ in modulating synaptic transmission, both positively and negatively, and the potential therapeutic implications of targeting these processes. Additionally, it explores the possibility that Aβ-induced synaptic and network alterations may contribute significantly to the cognitive and behavioral deficits observed in AD patients. The authors suggest that therapeutic strategies should focus on reducing Aβ levels and enhancing the brain's resistance to Aβ by targeting copathogenic factors or downstream mechanisms.