New research suggests that a diet high in salt may promote cognitive decline by destabilizing levels of the protein tau. Excessive levels of tau are a hallmark of dementia.
Dr. Giuseppe Faraco, an assistant professor of research in neuroscience in the Feil Family Brain and Mind Research Institute at Weill Cornell Medicine in New York, is the lead author of the new study, which appears in the journal
As Dr. Faraco and team explain in their paper, an excessive intake of salt has always had associations with poor cerebrovascular function, and high salt intake is an independent, well established risk factor for dementia.
But the more intriguing question is, how does excessive salt trigger dementia?
Previous research in rodents led by Dr. Faraco — together with Dr. Costantino Iadecola, director of the Feil Family Brain and Mind Research Institute and a co-author of the new study — started to elucidate this mechanism.
In the previous study, the researchers found that a diet high in sodium leads to dementia in mice by triggering the overproduction of a molecule that promotes inflammation.
The molecule, interleukin-17 (IL-17), stops brain cells from producing nitric oxide. Nitric oxide has the role of helping blood vessels to widen, which allows blood to flow. However, insufficient levels of nitric oxide can lead to restricted blood flow
In this mouse study, a high salt diet triggered high levels of IL-17, which in turn, lowered nitric oxide levels and reduced blood flow by 25%.
Building on this previous research, Dr. Faraco and team hypothesized in the new study that high levels of sodium would do the same thing — cause dementia by restricting the blood flow to the brain, an effect mediated by low nitric oxide.
However, the experiments revealed something unexpected.
Tau, not blood flow, caused dementia
The researchers fed 8-week old male and female mice either a regular diet or a diet enriched in sodium for 4–36 weeks.
The scientists performed behavioral, cerebrovascular, and molecular studies, which revealed that the low levels of nitric oxide that were induced by a high salt diet affected the levels of tau protein in the brain.
An excessive buildup of tau is a hallmark of Alzheimer's. Typically, tau supports neurons by stabilizing structures called microtubules, which transport nutrients to neurons' axons and dendrites. They are a part of the cytoskeleton, or "scaffolding," that supports neurons.
"Tau becoming unstable and coming off the cytoskeleton causes trouble," Dr. Iadecola explains.
The researcher adds that tau should not roam freely inside the cell because if it detaches from the cytoskeleton, it has the potential to build up in the brain, leading to cognitive difficulties.
In the study, the scientists found that nitric oxide "puts the brakes on activity caused by a series of enzymes that leads to tau disease pathology."
So, to further test the dynamic between nitric oxide, tau protein, and cognitive impairment, the scientists combined the high salt diet and restricted blood flow with an antibody that kept tau proteins in check.
As a result of the tau stabilizer, these mice exhibited normal cognitive functioning, despite having restricted blood flow. "This demonstrated that what's really causing the dementia was tau and not lack of blood flow," explains Dr. Iadecola.
These results led the researchers to believe that the link between dietary salt and tau pathology is a direct, causal one that does not depend on restricted blood flow.
'We've got to keep salt in check'
As the researchers write, "These findings identify a causal link between dietary salt, endothelial dysfunction, and tau pathology, independent of hemodynamic insufficiency."
Furthermore, "Avoidance of excessive salt intake and maintenance of vascular health may help to stave off the vascular and neurodegenerative pathologies," the authors conclude.
Dr. Iadecola warns about the dangers of high salt diets, suggesting that the findings in rodents are a good reminder of the risks to humans of high sodium intake.
However, more research is necessary to replicate the rodent findings in humans.
"[T]he stuff that is bad for us doesn't come from a saltshaker, it comes from processed food and restaurant food [...] We've got to keep salt in check. It can alter the blood vessels of the brain and do so in a vicious way."
Dr. Costantino Iadecola