Sodium Chloride Increases Aß Levels by Suppressing Aß Clearance in Cultured Cells.

ABSTRACT

Recent studies suggest that high-salt diet is associated with cognitive decline in human and mouse. The fact that genetic factors account for less than 50% cases of sporadic Alzheimer's disease (AD) highlights the important contribution of environmental factors, such as high-salt diet, in AD pathogenesis. However, whether and how high-salt diet fits the "amyloid cascade" hypothesis remains unexplored. Here, we show sodium chloride (NaCl) could increase Aß levels in the medium of HEK293 cells overexpressing amyloid precursor protein (APP) or C99 fragment. NaCl treatment dose not affect APP level, gamma secretase level or activity. Instead, NaCl treatment suppresses the capacity of cells to clear Aß and reduces Apolipoprotein E (ApoE) level. Finally, NaCl treated THP-1 or BV2 cells are inefficient in clearing Aß when co-cultured with rat primary neurons. Our study suggests that high-salt diet may increase AD risk by directly modulating Aß levels.