Lipoprotein lipase (LPL),a key enzyme in lipoprotein metabolism is found at high level in the hippocampus.Epidemiological studies show genetic polymorphisms of LPL associate with the risk and pathophysiological severity of AD,but the mechanism remains unknown.Using electron microscopy,we first demonstrate that LPL-deficient neonatal mice are severely depleted of pre-synaptic vesicles at hippocampal synapses.Consistent with the ultrastructural findings,biochemical analysis reveals that the protein level of synaptophysin,a synaptic vesicle marker is significantly decreased in these mice.Our results suggest that LPL is required to maintain a normal pool of synaptic vesicles at the pre-synaptic sites and that abnormality of LPL may contribute to AD by inducing synaptic dysfunction.