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Targeting BACE1 inhibition is therefore a therapeutic strategy for treating patients with Alzheimer's disease. However, several clinical trials using brain\u2010penetrable BACE1 inhibitors have failed due to a lack of efficacy. Previous studies, including our own, have shown that both global and neuron\u2010specific BACE1 inhibition in mice leads to impairments in synaptic strength and spine density. In this study, we investigate the effects of BACE1 inhibition on activity\u2010dependent synaptic vesicle exocytosis and endocytosis using a synapto\u2010pHluorin mouse model. Our results demonstrate impaired synaptic release in BACE1\u2010deficient mice. Furthermore, transcriptomic analysis reveals a significant downregulation of genes related to synapse structure and function. Pathway analysis suggests that BACE1 deficiency significantly downregulates neurexin\u2010neuroligin pathway, which can modulate docking and release of synaptic vesicles at the presynaptic compartment. 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