The article reviews the decade-long research on the role of amyloid β-protein (Aβ) oligomers in Alzheimer's disease (AD). It highlights that while Aβ has long been known to play a central role in AD, the focus has shifted from the cytotoxic effects of extracellular amyloid fibrils to the detrimental effects of soluble, pre-fibrillar Aβ assemblies. The review discusses the evidence for the toxicity of these soluble Aβ forms, including their presence in human brain and APP transgenic mice, their ability to disrupt synaptic function, and their synaptotoxic properties. It also explores the potential therapeutic strategies aimed at preventing the formation or neutralizing the toxicity of these Aβ oligomers, such as inhibiting Aβ production, up-regulating Aβ catabolism, and developing antibodies to target and remove Aβ assemblies. The article concludes by emphasizing the need for further research to better understand the mechanisms of Aβ oligomer toxicity and to develop more effective treatments for AD.The article reviews the decade-long research on the role of amyloid β-protein (Aβ) oligomers in Alzheimer's disease (AD). It highlights that while Aβ has long been known to play a central role in AD, the focus has shifted from the cytotoxic effects of extracellular amyloid fibrils to the detrimental effects of soluble, pre-fibrillar Aβ assemblies. The review discusses the evidence for the toxicity of these soluble Aβ forms, including their presence in human brain and APP transgenic mice, their ability to disrupt synaptic function, and their synaptotoxic properties. It also explores the potential therapeutic strategies aimed at preventing the formation or neutralizing the toxicity of these Aβ oligomers, such as inhibiting Aβ production, up-regulating Aβ catabolism, and developing antibodies to target and remove Aβ assemblies. The article concludes by emphasizing the need for further research to better understand the mechanisms of Aβ oligomer toxicity and to develop more effective treatments for AD.