Effect of High-Salt Diet on Memory and Behavior in Mice Expressing Human Apolipoprotein Epsilon-4 (APOE4) Allele

Apolipoprotein epsilon (APOE) is a small molecular protein that regulates lipid and lipoprotein homeostasis. Several reports demonstrated that apolipoprotein epsilon-4 allele (APOE4) expression significantly increases the genetic risk of Alzheimer's disease (AD) and chronic kidney disease. However, there is inconsistent evidence of the association of AD with dietary habits, especially salt intake. Therefore, we hypothesized that high dietary salt intake would exacerbate cognitive decline in mice expressing the human APOE4 allele. We used human APOE (APOE4 and APOE3) knock-in mice to test this hypothesis. Young adult male and female mice aged 5-7 months old (n = 18 in each group) were fed a 4% NaCl (high-salt) or a 0.1% NaCl (low-salt) diet for 4 weeks. Metabolic cage studies were used to assess 24 h measurements of food and water intake, and urine output. Spatial memory and learning were determined using the Barnes maze test. Both the APOE3 and APOE4 mice on a low-salt diet had significantly decreased urinary volume, and female mice had lower body weight. The APOE4 mice on the low-salt diet (0.1%) performed significantly better on the 72 h probe test as compared to the APOE4 mice on 4% salt diet. The results demonstrate an association among dietary salt, memory, and APOE4 genotype.