Lipid and associated proteins play an important role in causing Alzheimers disease (AD) and other forms of dementia.Both pre-clinical and clinical researches suggested that cholesterol-lowering medicines could meliorate the memory impairment in established AD.Lipoprotein lipase (LPL),an essential molecule in lipoprotein metabolism in tissues such as adipose tissue has also been detected in the brain.Although previous studies suggested the possible relationship between LPL mutation and dementia,how LPL in brain influences learning and memory is unknown.Here,we used behavior tests,immunohistochemistry,western blotting,transmission electron microscopy (TEM) and other methods to investigate the mechanism(s) of tiffs memory impairment,using the LPL-Knockout mouse model.We first found that LPL-deficient mice had severe hippocampus-dependent memory impairment with behavior tests of radial ann water maze and step-down inhibitory avoidance.And interestingly,remarkable decrease of pre-synaptic vesicles as well as their marker synaptophysin was observed in the hippocampi from this kind of animals,but there was no significant neuron loss.Our investigation established the animal model of memory impairment with LPL deficiency for the first time.And the decrease of pre-synaptic vesicles caused by the imbalance of lipid homeostasis in brain might be the main reason of memory impairment in LPL-KO mice.