The article discusses the role of soluble oligomers of amyloid β-protein (Aβ) in the development of Alzheimer's disease (AD). It highlights that elevated levels of Aβ42 monomers can form soluble oligomers that diffuse into synaptic clefts and disrupt synaptic plasticity, particularly long-term potentiation (LTP), in both in vitro and in vivo models. The study identifies APP-expressing cell lines that produce low-n oligomers, which are released into the medium and exhibit potent inhibitory effects on hippocampal LTP. These oligomers also decrease dendritic spine density in organotypic hippocampal slice cultures, a process that can be prevented by Aβ antibodies or small-molecule modulators of Aβ aggregation. The research suggests that these naturally secreted Aβ oligomers play a crucial role in early synaptic dysfunction and memory impairment in AD, providing a potential therapeutic target for the disease.The article discusses the role of soluble oligomers of amyloid β-protein (Aβ) in the development of Alzheimer's disease (AD). It highlights that elevated levels of Aβ42 monomers can form soluble oligomers that diffuse into synaptic clefts and disrupt synaptic plasticity, particularly long-term potentiation (LTP), in both in vitro and in vivo models. The study identifies APP-expressing cell lines that produce low-n oligomers, which are released into the medium and exhibit potent inhibitory effects on hippocampal LTP. These oligomers also decrease dendritic spine density in organotypic hippocampal slice cultures, a process that can be prevented by Aβ antibodies or small-molecule modulators of Aβ aggregation. The research suggests that these naturally secreted Aβ oligomers play a crucial role in early synaptic dysfunction and memory impairment in AD, providing a potential therapeutic target for the disease.