High-Salt Diet Mediated Regulation of Salt Transporters in Kidney and Brain of Apolipoprotein ε4 Expressing Mice

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Introduction: Increasing studies suggest that high blood pressure is a risk factor for the development of Alzheimer’s Disease (AD). Studies have failed to look at differing etiologies of hypertension in the development of AD, specifically age-dependent salt-sensitive hypertension. Salt-sensitive hypertension is essential to study due to the large health concern of the over-consumption of salt in diets and the high prevalence of salt-sensitive individuals. Aim: This study aims to elucidate the relationship of salt-sensitive hypertension on the expression of salt and water transporters in the kidneys and brain of APOE3 and APOE4 knock-in mice. Methods: 5- to 7-month-old mice were given a control (CONT) diet (0.4% NaCl) for one week. Baseline urinary volume, Na + , K + , and Cl - were collected. Mice were randomly assigned to two groups, low salt diet (0.1% NaCl) (LSD) and high salt diet (4.0% NaCl) (HSD), and given the diets for one month. Following the study's conclusion, we collected 24 urine samples to measure urinary volume, Na + , K + , and Cl - . Serum samples were collected for Na + , K + , and Cl - concentrations. Kidneys and the brain were used to determine the expression of sodium transporters and water channels (see results) by western blot. Results: In the brain, a high dietary salt had a slight increase in NKCC1 expression and increased NKA-a1 expression in both male and female mice carrying the APOE4 allele. In the kidney, high dietary salt caused a decrease in the expression of Na + /K + -ATPase a1, NKCC2, and NCC in APOE3 males and females. Na + /K + -ATPase a1, NKCC2, and NCC expression increased in both male and female mice carrying the APOE4 allele. Aqp2 expression was increased in male APOE4 mice but not in the female mice. Discussion: A high salt diet decreased the expression of salt transporters in the kidney and brain in APOE3 allele-carrying mice but increased in mice carrying the APOE4 allele. The increased expression of salt transporters in APOE4 allele-carrying mice may contribute to the changes in brain size in AD and the retention of salt and water by the kidneys. HU CoM Bridge Grant, Syed Khundmiri, PhD, (PI) Jahn O’Neil, PhD (Co-PI) 2021-22 Karen Toffler Charitable Trust 2024 Scholar award, Jahn O’Neil, PhD (PI) This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.

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