Low-density lipoprotein receptor-knockout mice display impaired spatial memory associated with a decreased synaptic density in the hippocampus

The low-density lipoprotein receptor (LDLR) is the first described receptor for apolipoprotein E (apoE). We hypothesize that the absence of the LDLR, similar to the absence of apoE, results in impaired learning and memory processes. Six-month-old homozygous Ldlr−/− and wild-type littermates (Ldlr+/+), maintained on a standard lab chow diet, were used. Unlike humans, Ldlr−/− mice, under these conditions, do not develop atherosclerosis. The results of the Morris water escape task revealed an impaired spatial memory in the Ldlr−/− mice in comparison with Ldlr+/+ mice. Also in a T-maze task, the working memory performance of the Ldlr−/− mice was impaired. Furthermore, Ldlr−/− mice, in comparison with Ldlr+/+ mice, display a decreased number of synaptophysin-immunoreactive presynaptic boutons in the hippocampus CA1. In conclusion, the results show in mice deficiency for the LDLR results in impaired hippocampal-dependent memory functions. A decrease in the number of presynaptic boutons may underlay these behavioral alterations. Therefore, the LDLR may be an important receptor for apoE in the central nervous system.