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High SALT: A Risk Factor for Alzheimer’s Disease

John Lopes Ph.D.

 Evolutionary process has naturally integrated salt, an absolute nutrient ingredient, with taste buds. Since millennium salt has been used as preservative for pickles, meat, and fish to prevent spoilage by microorganisms. Even animals crave salt. An elephant matriarch leads the herd several miles to salt rocks to get dietary complement. Cockatiels fly hundreds of miles to distant salty mountain peaks to get their dietary salt requirement.

Although salt has been long associated with high blood pressure. In a hurried lifestyle, it is difficult to get low salt hamburgers, fries, ham sandwiches, hot dogs, pizza and more fast food items. Even in regular sit-down restaurants it is difficult to order a low salt meal.

Recent findings suggest that in addition to high blood pressure, high salt may can also cause stroke, declining cognition and memories. Dr. Costantino Iadecola and a team of researchers at Weill Cornell Medicine found that mice fed with high salt diets had trouble recognizing novel objects and navigating through a maze. They found that high salt diet reduced the level of enzyme (nitic oxide synthase) that produces NO (nitric oxide). Nitric oxide helps blood vessels to relax resulting in increased blood flow. A high salt diet stimulates TH-17 cells in the small intestine to produce circulating plasma interleukin-17 which in turn inhibits nitric oxide synthase in cerebral endothelial cell (Giuseppe Faraco, et al, Nature Neuroscience).. Thus, high salt in diet inactivates Endothelial Nitric Oxide Synthase in endothelial cells

The scientists found that reduced thinking and memory function was directly related to lower nitric oxide levels. After being placed on a high salt diet for 12 to 36 weeks the mice were tested for cognitive functions and their brains were examined for molecular changes.

 Mice on the high salt diet had reduced blood flow to the brain resulting in poorer performance on a standard set of cognitive tasks. Further investigations by the researches showed that only reduced blood flow to the brain did not entirely explain reduced cognition in the mice. Advanced molecular studies showed that the effects of high salt on the phosphorylation of the protein tau were mediated through nitic oxide levels, and not through the reduction in blood flow. In other words nitic oxide prevents phosphorylation and high salt inhibits the eNOS enzyme that produces nitic oxide.

 It has been known that a protein called TAU accumulates in the brains of people with Alzheimer’s disease. The research team found that a high salt diet reduces the level of nitric oxide which indirectly results in adding phosphate groups (phosphorylation) to TAU. When phosphorylated TAU protein clumps together in the brains. Clumps of TAU are linked with some dementias, such as Alzheimer’s disease.

Previous study by the team has shown that even with high salt diets mice, fed with a compound that increases production of nitric oxide, can overcome the accumulation of phosphorylation of tau. Further studies with mice which lacked TAU had no deleterious effect to cognitive tasks with high salt diet.