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. (C) 2004 Elsevier Inc. All rights reserved.