Alzheimer's disease (AD) is a neurodegenerative disorder characterized by the accumulation of amyloid-β (Aβ) peptides, which are implicated in synaptic dysfunction and cognitive decline. Recent studies suggest that Aβ acts as a dual regulator of synaptic activity, enhancing presynaptic function at low concentrations and suppressing postsynaptic function at high concentrations. Pathological Aβ accumulation leads to synaptic depression, abnormal neuronal circuit activity, and epileptiform discharges, contributing to network instability. Aβ-induced dysfunction of inhibitory interneurons may increase excitatory synchrony, further destabilizing neural networks. Strategies to block Aβ effects could prevent cognitive decline in AD. However, challenges remain in understanding the precise mechanisms and developing effective therapies. Aβ oligomers are more harmful than fibrils in disrupting synaptic function and network activity. Aβ affects synaptic transmission by modulating NMDAR and AMPAR currents, with presynaptic effects mediated by α7-nAChR activation. Aβ can enhance presynaptic glutamatergic release in low-activity neurons but not in high-activity neurons. Aβ also induces long-term depression (LTD) by activating mGluRs and NMDARs, which may underlie Aβ-induced impairments in long-term potentiation (LTP). These effects are linked to synaptic loss and cognitive deficits. Elevated Aβ levels disrupt neuronal circuits and networks, leading to abnormal activity patterns and epileptiform discharges. Aβ-induced synaptic depression may result from increased NMDAR activation, receptor desensitization, and internalization, as well as activation of perisynaptic NMDARs and mGluRs. These changes contribute to cognitive impairments by reducing the time neural networks spend in activity patterns that support normal cognitive functions. GABAergic dysfunction is a key factor in Aβ-induced network dysfunction, with impaired GABA release and reduced inhibition in hippocampal circuits. Aβ may also affect non-neuronal functions, such as astroglial calcium signaling, which can release glutamate and activate extrasynaptic NMDARs, promoting neuronal excitability. Inflammatory responses from microglia may further exacerbate network dysfunction. Despite advances in understanding Aβ's role in AD, several unresolved issues remain, including the need for better tools to detect and manipulate specific Aβ assemblies in vivo, determining which neurons and synapses are most affected, and clarifying the relationship between Aβ-induced changes at the synaptic, circuit, and network levels and cognitive function. Addressing these issues is crucial for developing effective therapies for AD.Alzheimer's disease (AD) is a neurodegenerative disorder characterized by the accumulation of amyloid-β (Aβ) peptides, which are implicated in synaptic dysfunction and cognitive decline. Recent studies suggest that Aβ acts as a dual regulator of synaptic activity, enhancing presynaptic function at low concentrations and suppressing postsynaptic function at high concentrations. Pathological Aβ accumulation leads to synaptic depression, abnormal neuronal circuit activity, and epileptiform discharges, contributing to network instability. Aβ-induced dysfunction of inhibitory interneurons may increase excitatory synchrony, further destabilizing neural networks. Strategies to block Aβ effects could prevent cognitive decline in AD. However, challenges remain in understanding the precise mechanisms and developing effective therapies. Aβ oligomers are more harmful than fibrils in disrupting synaptic function and network activity. Aβ affects synaptic transmission by modulating NMDAR and AMPAR currents, with presynaptic effects mediated by α7-nAChR activation. Aβ can enhance presynaptic glutamatergic release in low-activity neurons but not in high-activity neurons. Aβ also induces long-term depression (LTD) by activating mGluRs and NMDARs, which may underlie Aβ-induced impairments in long-term potentiation (LTP). These effects are linked to synaptic loss and cognitive deficits. Elevated Aβ levels disrupt neuronal circuits and networks, leading to abnormal activity patterns and epileptiform discharges. Aβ-induced synaptic depression may result from increased NMDAR activation, receptor desensitization, and internalization, as well as activation of perisynaptic NMDARs and mGluRs. These changes contribute to cognitive impairments by reducing the time neural networks spend in activity patterns that support normal cognitive functions. GABAergic dysfunction is a key factor in Aβ-induced network dysfunction, with impaired GABA release and reduced inhibition in hippocampal circuits. Aβ may also affect non-neuronal functions, such as astroglial calcium signaling, which can release glutamate and activate extrasynaptic NMDARs, promoting neuronal excitability. Inflammatory responses from microglia may further exacerbate network dysfunction. Despite advances in understanding Aβ's role in AD, several unresolved issues remain, including the need for better tools to detect and manipulate specific Aβ assemblies in vivo, determining which neurons and synapses are most affected, and clarifying the relationship between Aβ-induced changes at the synaptic, circuit, and network levels and cognitive function. Addressing these issues is crucial for developing effective therapies for AD.