This study explores how amyloid beta oligomers (AβO) in Alzheimer's disease (AD) disrupt a process called endocannabinoid (eCB) mobilization, crucial for learning and memory. AβO reduce levels of the protein PLCβ1 in the hippocampus, impairing the brain's ability to strengthen connections between cells, called synaptic plasticity, essential for memory formation. This study found that using a compound (m-3M3FBS) to activate PLCβ1 in brain slices restored this process and improved synaptic plasticity. In 5XFAD mouse model of AD, injecting m-3M3FBS into the hippocampus restored PLCβ1 levels and improved contextual fear memory comparable to the level observed in healthy control mice. This suggests that targeting PLCβ1 could lead to new treatments for memory loss in AD.