Re: Red meat, science and buffets (Oct. 5 column by Sylvain Charlebois).

Charlebois makes much of the Annals of Internal Medicine study which claims to have evidence that red and processed meats arent as unhealthy as most doctors are now saying.

There are, however, cogent criticisms of that study:

From a Sep. 30 Washington Post article, by Laura Reiley: Another critic of the study, Walter Willett, professor of epidemiology and nutrition at Harvard T.H. Chan School of Public Health, said the Annals of Internal Medicine study also ignored solid science in the arena.

. Willett says the panels conclusions and recommendations do not reflect the studys findings. Their meta-analyses of large cohorts showed that dietary patterns with a moderate reduction in red and processed meat consumption were associated with lower total mortality by 13 per cent. If a drug brought down the number of deaths to that degree, he says, it would be heralded as a success.

.... Bonnie Liebman, director of nutrition at the Center for Science in the Public Interest, says one of the studys chief flaws is its reliance on the Womens Health Initiative study, a huge analysis of 48,000 women that had half the participants eating their regular diet and half eating a low-fat diet, which in many cases led to a half-an-ounce difference in meat consumption per day in the two groups, about a fifth of a hamburger. No surprise, there wasnt much difference in outcomes. Because of its size, the womens study may have skewed the overall results of the Annals of Internal Medicine report.

In other words, the study to which Mr. Charlebois refers did in fact show a 13 per cent reduction in mortality from a moderate reduction (note:not elimination) of red and processed meat in the regular diet. But the study doesnt support the conclusion that even those eating, say, 15 servings a week of red meat (the U.S. average), or more, can safely carry on.

Neil Bell, Baddeck

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LETTER: Hold that burger | Regional-Perspectives | Opinion - The Guardian

On the ultraprocessed diet, the subjects on average consumed 500 more calories a day and gained two pounds. A possible reason: The participants levels of PYY, a hormone that suppresses appetite, were lower on it, while the levels of ghrelin, a hunger-stimulating hormone, were higher. Because the nutrients were constant, the researchers theorize, the processing itself may somehow trigger the hormonal changes. In a paper published in Cell Metabolism in May, they write that limiting consumption of ultraprocessed food may be an effective strategy for obesity prevention and treatment.

The results seemed to reinforce a general, even obvious consensus among nutrition researchers and yet they generated criticism anyway, much of which highlights fundamental challenges in designing dietary experiments. One charge leveled against Halls study, for example: It was too short to observe metabolic and behavioral changes that often take place more than two weeks after a new diet is started. But as Hall points out, it would have been hard to recruit people to live longer under such strict conditions. Whats more, outside the lab, subjects often fail to stick to a diet precisely, and their habits are so variable that it can be tricky to tell for sure whether the meal plan in question is having an effect. Yet its impossible to say whether a diet that works in the lab will succeed unless you can study it in real life. I do think there are ways to get accurate data in free-living people, Dr. Lydia Bazzano, an epidemiologist at the Tulane University School of Public Health and Tropical Medicine, says. If you cant, were all sunk.

At stake is the question of how government agencies and other institutions should deploy limited resources to address a catastrophic national health problem. How should dietary research be conducted in order to ultimately produce results that will be most useful to the public? For instance, most clinical trials are set up, as Halls was, to answer an either-or question say, Does this diet cause weight loss? traditionally by comparing an experimental group with a control. But in nutrition, the answer is often it depends. To try to understand how multiple factors might influence a diets success, Mayer-Davis and others are working on sequential, multiple assignment, randomized trials (SMARTs), whose subjects, in her words, move from one treatment to another one to another one over time, depending on how theyre doing. In a continuing 10-month N.I.H.-funded pilot study, one of the first to use this method to assess dietary strategies, she and colleagues randomly assigned volunteers between 19 and 30 with Type 1 diabetes who are overweight to one of three diets: a low-fat plan or a low-carbohydrate plan, both of which were low in calories, or a Mediterranean-style plan. At three and six months, if they dont like the diet, havent lost 2 percent body weight from their last check-in or are having trouble maintaining their blood-sugar levels, they will move to a different plan. Afterward, statistical analyses will determine what characteristics, including those related to lifestyle, were associated with success, or a lack thereof, for each treatment. Eventually, researchers hope, that sort of information will allow clinicians or even a smartphone app to create a personalized diet.

Of course, even personalized diets would still need to be adhered to, and this raises another quandary. Fundamentally, especially in the Western world, our diet is fairly unhealthy, Corby Martin of the Pennington Biomedical Research Center, at Louisiana State University, says. With really broad strokes we could improve our health by making modifications to our diet that everyone could make. So why havent we? And what are we more likely to follow: a diet that is more personalized than past ones have been or, as in Halls formulation, more general?

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Why Isnt There a Diet That Works for Everyone? - The New York Times

Singer Adele has been looking great recently, losing 14 pounds since her split from her husband, Simon Konecki, earlier this year. The singer has always had a curvy figure and a firm attitude of body positivity.

Ive never wanted to look like models on the cover of magazines, she told People in 2012. I represent the majority of women and Im very proud of that.

They say looking good is the greatest form of revenge. If that is true, Adeles vengeance is complete.

An insider at the time of the couples separation told E! News, Their marriage was clearly working for a very long time. Whenever she was out at big openings and special events, he was usually with her, and they looked really just happy together and in love. They were into the marriage pretty much until they decided this just isnt working anymore.

Adele had already made her health a priority before the birth of her son, Angelo, in 2012, and lost weight at that time as well. The multiple-Grammy winner has always looked beautiful, but her current additional weight loss has given her a healthful glow.

I was trying to get some stamina for my tour, so I lost a bit of weight. She told Vogue magazine in 2016: Now I fit into normal, off-the-shelf clothes which is a really big problem for me!

Adele has never been one to enjoy dieting and exercise but got serious about her health with the birth of her son Angelo, now 6 years old.

Recently, she has been following a diet that works for her and that has given her results. Its called the Sirtfood Diet and while it includes whole, lower-calorie food, proteins, fruits, and green juices, its pretty strict. Followers of the diet are only allowed 1000 calories in the first few days of the diets first phase. The final days of the first phase allow followers to have up to 1500 calories.

Clearly, its not for the faint of heart, but judging by Adeles results, it works.

Its taken Adele time to get used to the idea of exercising regularly. She opened up to Rolling Stone in 2015 about her exercise routine at the time.

I mainly moan. Im not, like,skippingto the f***ing gym. I dont enjoy it. I do like doing weights {and] dont like looking in the mirror. Blood vessels burst on my face really easily, so Im so conscious when Im lifting weights not to let them burst in my face. And if I dont tour, youll catch me back down at the Chinese.

A source told Us Weekly in Julythat the Rolling in the Deep singer started a fitness regimen after hiring a personal trainer in L.A. She does 60-minute sessions that include cardio, circuit training, and Pilates. Shes found a routine thats working for her and is enjoying it more.

Read more: 15 Celebrities Who Went on Extreme Diets for a Movie Role

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Adele Swears By This Diet and Exercise Regimen - Showbiz Cheat Sheet

FROM putting recruits through their paces in SAS Who Dares Wins to climbing Mount Everest - Ant Middleton knows a thing or two about fitness.

The ex-military man, 38, has also starred on the front cover of Men's Health and has made a career out of pushing his body to its limit.

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Here, Ant, who is the face of Garmin, talks us through his top tips to getting in shape - without splurging your hard-earned money on an expensive gym membership.

He told The Sun Online the key is balance when it comes to both dieting and exercise.

As someone who does most of his exercise in the harsh outdoors, Ant says it's a myth that the gym is the only place you can get fit.

In an exclusive interview, Ant says: "You also dont need a gym membership to stay in shape, just go out into the garden or a local park and do some circuits training.

"Anything that raises your heart rate will help keep you in shape."

It may sometimes be tricky to fit a workout into your busy week, but Ant says making a plan for your fitness schedule can really make a difference.

He also emphasises not to worry if you do miss out on exercise days sometimes.

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Ant says: "This is obviously not always possible but if you plan to work out seven days a week, you will probably end up working out four days a week which is definitely enough to stay in shape.

"If you plan for four days and it doesnt work out, because life just does get in the way sometimes (!), you will start to miss out on exercise days."

He may look as though he's solid protein, but Ant urges those wanting to lose weight to focus on "balance".

"I think you just need to listen to your body, I personally eat a lot of carbs and protein but this isnt necessarily right for everyone," he tells The Sun Online.

"As long as you have a balanced diet, you cant really go too wrong."

Ant is keen to emphasise the importance of working on your mental as well as your physical health.

Ant, who runs Mind Over Muscle day camps across the country, says: "Physical and physiological simulation comes hand in hand, if one suffers it tends to have a detrimental effect on the other.

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"We must challenge ourselves psychologically on a daily basis, as well as physically at least every other day, even if it just walking the dog or walking to the shop for that pint of milk.

"Physical activity has always been part of my life and once it becomes routine in your life thats when it becomes a lifestyle and you cant do without it."

Dieting can not only be draining but also have a negative impact on your mental health if you're trying to lose weight.

"I lead a sustainable lifestyle and tend not to diet, even when I lose extreme weight," Ant says.

"I let my body gradually build its way back up to the weight that I function efficiently at on a day to day basis."

Ant says if you're trying to shed the pounds or boost your fitness, not to rush.

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He says: "Its all a gradual process, these extreme weight drops and gains arent good for the body so I let natural run its course."

Ant recommends investing in a fitness watch which can help you track your progress.

Ant says he's a fan of the Garmin Fenix 6 watch as it means he can plan running routes wherever he is in the country.

The watch also comes with other features including full topographic maps and GPS, as well as PacePro which gives you a full view of elevation changes when out running or training.

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Ant says: "I have had a relationship with Garmin for the past 15 years, since I was in the military to now, the brand is always evolving and changing with the times which is something I love about it.

"One feature that has always helped with my training is the GPS system.

"It means I can go on a run wherever I am in the country and they will create a route for me, so handy when you are on tour and still trying to keep fit."

Read more:
Weight loss: Ditch the gym AND fad diets Ant Middletons easy tips to get in shape - The Sun

It was a challenge unlike any other the chef-turned-graduate student had faced: Vayu Maini Rekdal had to create a menu where every ingredient could be eaten either raw or cooked. No pickling was allowed, nor fermented toppings like soy sauce or miso. Nothing could be processed in any way, so things like tofu were out. And the more sweet potatoes he could serve up, the better.

It was extremely challenging, said Mr. Rekdal, a chemistry graduate student at Harvard.

Rising to the occasion, Mr. Rekdal concocted chia seed breakfast puddings that could be cooked or chilled. He made raw and cooked pea-sweet potato-tahini patties. And for three days, eight volunteers dined on the unusual menu, providing stool samples to assist in research that could eventually help illuminate the evolution of the human microbiome.

The work was led by Rachel Carmody, a professor of human evolution at Harvard, and Peter Turnbaugh, a professor of microbiology at the University of California, San Francisco. They were studying the gut microbiome, the collection of microbes that live in our intestines and influence our immune system and various other parts of our biology, as well as help us digest food.

They had discovered that mice, eating a diet of starchy foods like sweet potatoes, developed vastly different microbiomes, depending on whether their food had been cooked or served raw. A switch from one to the other provoked a rapid shift in their guts microbial inhabitants.

Now, they wanted to see if the same was true with humans.

The results of the experiment appear in a paper published last month in Nature Microbiology. Although the sample size was small, and the effect was not as strong as in mice, peoples microbiomes do seem to shift on a raw diet, and very rapidly. While the human study was very short, it raises intriguing questions about whether starting to eat cooked food, eons ago, shaped the evolution of the organisms that live inside us, and whether our bugs may have helped us survive times of scarcity.

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As a graduate student, Dr. Carmody found that mice fed cooked diets quickly grew plump. Cooking alters the structure of many molecules, making more energy available to the mice. But she was also interested in the microbial community living in the mouse gut, which helps digest food and interacts with its hosts biology in a variety of ways.

In the new paper, she and her collaborators found that feeding mice meat that was raw or cooked changed little about their microbiomes. But with sweet potatoes, meant to stand in for tubers that early humans might have eaten, it was a different story.

Cooking produced significant changes, affecting the kinds of microbes that thrived and which genes they used.

The scientists traced the effect to the sweet potatos starches, which are difficult for mammals to digest raw but become more easily digestible once cooked. Depending on which kind of starch molecules arrive in the large intestine, different groups of microbes might take on the disposal job and subsequently surge in numbers.

Like any ecosystem, if you dramatically change foodstuffs coming into it, some species will thrive over others, Dr. Carmody said.

The researchers also found that raw sweet potatoes inflicted an impressive amount of damage on the microbiome of the mouse gut, similar to what occurs in mice fed an antibiotic. That may result from antimicrobial compounds in the sweet potato, which may be inactivated by cooking.

If cooking, at least of starches, can alter the ecology of the gut, then have humans been shaping our microbiomes ever since we learned to put prehistoric tubers in the fire? If our ancestors did eat these kinds of foods, and switched to cooking them, it may be that some tasks that used to be handled by gut microbes were no longer necessary, says Stephanie Schnorr, a biological anthropologist at the University of Nevada, Las Vegas, who was not involved in the study. As a result, the bacteria might have lost the related genes or gained new roles.

The ability of the guts microbial residents to shift themselves so dramatically even in the short term may have had other benefits for their hosts. If microbiomes can retool themselves on little notice to handle changes in diet, they may have helped early humans cope with lean days where tubers were the only foods or times when only meat was on the menu.

The microbiome could essentially help us, within 24 hours, maximize our ability to digest nutrients even on a low-quality diet, Dr. Carmody said.

Still, the extent to which humans and their live-in digestion engines evolved together is debated. Mice given human microbiomes are generally healthy, suggesting that a host and its microbes dont fit together like a lock and key, honed by eons of mutual evolution. However, in some situations, like when a mouse gets sick, it is more likely to recover when it has its own microbiome. That may imply that there has been some co-evolution between the organism and its microbiome, Dr. Carmody said.

The interaction between host and microbes is complex, and longer studies with more people eating a raw or cooked diet would be necessary to probe how such a dietary change affects the microbiome and its host in the longer term.

People actually did enjoy the menu, by and large, Mr. Rekdal said, which included salads of mushrooms, sweet potato and cauliflower, either roasted or raw, and smoothies of cooked or raw fruit in addition to the puddings and patties. Some of the raw items werent wildly popular, but he has received many requests for the chia pudding recipe.

He sees the study as helping advance our understanding of cooking, a particularly ancient kind of applied chemistry.

Its a form of science, he said, that humans have been practicing for thousands and thousands of years.

Excerpt from:
When the Menu Turns Raw, Your Gut Microbes Know What to Do - The New York Times

News Release

Wednesday, October 23, 2019

NIH-funded mouse study links high sodium consumption with a group of dementias.

High levels of dietary salt can activate a pathway in the brain to cause cognitive impairment, according to a new study. The paper, which was published in Nature, shows that this effect is not due to a loss in blood flow to the brain as originally thought, but rather to clumps of a protein linked to several forms of dementia in humans. The research was funded by the National Institute of Neurological Disorders and Stroke (NINDS), part of the National Institutes of Health.

This study continues the important story of the effects of a high-salt diet on the brain, said Jim Koenig, Ph.D., program director at NINDS. This work in mice reveals a new target for therapies aimed at brain blood vessel dysfunction.

In a previous research study, scientists led by Costantino Iadecola, M.D., director and chair of the Feil Family Brain and Mind Research Institute at Weill Cornell Medicine in New York City, showed that mice that ate a diet high in sodium began to show symptoms of dementia due to changes that occurred in the gut. The diet also produced a drop in the flow of blood to the brain, which they thought would be the cause of the dementia symptoms. However, when they looked more closely, they found instead that a buildup of a protein called tau in the brain was the cause.

This result was completely unexpected, said Dr. Iadecola. We knew that a high-salt diet produced dementia-like symptoms in mice, and we went in thinking the culprit would be reduced blood flow to the brain. It turned out that wasnt the case at all.

The original link found between high salt diets and brain blood flow was a decrease in the production of nitric oxide (NO) in cells making up blood vessels in the brain, caused by a reduction in the function of the enzyme eNOS. Blood flow in the brain increases when NO is present; however, NO generated from blood vessel cells has several other functions in the brain. These include being part of a molecular pathway connected to tau that, in the absence of sufficient NO, can modify tau protein in a way that causes it to clump together to form aggregates.

In a family of diseases called tauopathies, it is these tau aggregates that interfere with the proper function of brain cells, which can lead to cognitive impairment and eventually dementia. When mice consumed the high-salt diet in this study, their brains also showed evidence of tau aggregates that coincided with reduced cognitive abilities.

The researchers further showed that tau was the important factor behind these effects by studying mice that had their gene for tau deleted. These mice showed a similar drop in brain blood flow, but because they could not make tau protein, they did not form tau aggregates, nor did they show a decrease in their cognitive abilities. Similar results were observed with an antibody against tau.

The take-home message here is that is that while there is a reduction in blood flow to the brains of mice that eat a high-salt diet, it really is tau that is causing the loss in cognitive abilities. The effect of reduced flow really is inconsequential in this setting, said Dr. Iadecola.

He noted this result could have been predicted. After eating a high amount of sodium, the mice had about a 25% decrease in blood flow. This drop is similar to what is seen in people after drinking a cup of coffee. Evidence suggests it actually takes about a 50% drop before the brain can no longer compensate and cognitive effects are seen.

Although Dr. Iadecola points out that the salt content consumed by the mice in this study is eight to 16 times higher than normal and is likely to be more than a person would consume in a single day, their findings provide important links between diet, the blood vessels of the brain, and cognition.

Our results highlight the importance of thinking beyond blood flow when treating disorders affecting the brains blood vessels, said Dr. Iadecola.

This work was supported by NINDS (NS089323, NS095441), the Cure Alzheimers Fund, the American Heart Foundation, and the Feil Family Foundation.

This news release describes a basic research finding. Basic research increases our understanding of human behavior and biology, which is foundational to advancing new and better ways to prevent, diagnose, and treat disease. Science is an unpredictable and incremental process each research advance builds on past discoveries, often in unexpected ways. Most clinical advances would not be possible without the knowledge of fundamental basic research.

NINDSis the nations leading funder of research on the brain and nervous system.The mission of NINDS is to seek fundamental knowledge about the brain and nervous system and to use that knowledge to reduce the burden of neurological disease.

About the National Institutes of Health (NIH):NIH, the nation's medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit http://www.nih.gov.

NIHTurning Discovery Into Health

Faraco G. et al. Dietary salt promotes cognitive impairment through tau phosphorylation. Nature. October 23, 2019. DOI: 10.1038/s41586-019-1688-z

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Continue reading here:
Pathogenic tau and cognitive impairment are precipitated by a high-salt diet - National Institutes of Health

25 Oct 2019

Too much salty food wreaks havoc on the cardiovascular system, raising blood pressure, damaging small blood vessels, and limiting perfusion into the brain. But is this why salt increases the chances of cognitive impairment? Not so fast. At this years Society for Neuroscience meeting, held October 1923 in Chicago, Giuseppe Faraco from Costantino Iadecolas lab at Feil Family Brain and Mind Research Institute of Weill Cornell Medicine, New York, reported that learning and memory deficits in mice chowing on a high-salt diet correlated with phosphorylation of tau, not with damage to the brains blood vessels. The study, published October 23 in Nature, links reduced nitric oxide in blood vessel walls to activation of kinases that modify tau. The findings present a new twist in the well-known link between cardiovascular disease and risk for cognitive decline.

Admittedly, at eight to16 times the norm, the amount of salt the mice consumed exceeds all but the very highest equivalents in which people might indulge. Still, researchers found the results thought-provoking. However artificial the diet, this highlights that salt has effects independent of high blood pressure and that salt is a risk factor in its own right, said Joanna Wardlaw, University of Edinburgh. Wardlaw thinks the mechanism may explain some clinical observations. Weve seen in studies of small stroke that despite treating high blood pressure, people continue to get worse clinically and on their brain scans, she told Alzforum. We need to think about the role of other common risk factors, including dietary salt.

Li-Huei Tsai and Joel Blanchard, Massachusetts Institute of Technology, found the Columbia groups work fascinating. They illustrate that neuronal cells and the cerebrovasculature have dynamic molecular and biochemical interactions that clearly influence neurodegenerative pathologies, they wrote to Alzforum (full comment below). Faraco found the salt-induced reduction in nitric oxide (NO) boosted levels of p25, which activates the kinase Cdk5. Tsai has linked p25/Cdk5 to neurodegeneration (Dec 1999 news).

Pickled. AT8 immunostaining detects phosphorylated tau in the brains of mice fed a high-salt diet (right), but not in brains of mice on normal chow (left). [Courtesy of Giuseppe Faraco et al., Nature.]

The NO link most intrigued Zvonimir Katusic, Mayo Clinic, Rochester, Minnesota, as well. Susan Austin in Katusics lab found that knocking out endothelial nitric oxide synthase (eNOS) increases processing of A precursor protein and impairs learning and memory, and most recently that it boosts p25 and phosphorylation of tau (Austin et al., 2010; Austin et al., 2013; Katusic and Austin et al., 2016). In Chicago, Austin reported that microglia from eNOS knockouts ramp up production of ADAM17, the primary sheddase for TREM2, and tone down production of the anti-inflammatory cytokine IL-10. It appears release of NO by the endothelium is an important control mechanism for the brain, said Katusic.

The plot gets thicker. The effect of high salt may not start in the endothelial cells of the brain, but in immune cells of the gut. Last year Faraco reported that a high-salt diet elicits a flood of interleukin-17 from T helper cells in the intestine. That IL-17 lead to a dearth of endothelial NO and impaired memory (Jan 2018 news). The IL-17 reduced cerebral blood flow by about 25 percent, but Faraco considers this insufficient to cause the memory impairment. Since tau pathology has been linked to cerebrovascular disease, he decided to see if a high-salt diet affected the microtubule binding protein.

Faraco put normal C56/Bl6 mice on a diet comprising 8 percent NaCl. This is 16 times the normal amount of salt in mouse chow; seawater is about 3.5 percent NaCl. The mice ate as much food as usual, but over the next 36 weeks, levels of phosphorylated tau rose. AT8 immunoreactivity peaked after 24 weeks, RZ3 immunoreactivity after 36 weeks. These antibodies recognize tau phosphorylation at serine 202/threonine 205 and threonine 231, respectively. Hyperphosphorylation of tau was detected in both male and female mice, and in mice on a 4 percent NaCl diet, albeit only AT8 staining in that case. Faraco found similar tau changes when he fed 8 percent salt to Tg2576 mice, which model amyloidosis. Levels of A were unaffected.

What about neurofibrillary tangles? Faraco found none in any of the mice, but levels of insoluble tau released by formic acid did increase slightly in the cortices and hippocampi of mice on the high-salt diet.

In parallel with the tau phosphorylation, C57/Bl6 mice began having learning and memory problems. They struggled to recognize novel objects in their cages and had trouble finding the escape route in the Barnes maze. The deficits modestly correlated with AT8 binding in the cortex and hippocampus.

Was hyperphosphorylation of tau to blame? The authors tested this in two ways. They administered anti-tau antibodies to wild-type mice on high salt, and they fed high salt to tau knockouts. In both cases the animals performed as well as mice on normal chow, despite hypoperfusion of the brain, suggesting that indeed it was the tau that drove the cognitive decline due to the salt and not reduced blood flow.

Given Katusics prior data suggesting links between endothelial NO and tau phosphorylation, Faraco tested if he could stop the protein modification with L-arginine, a precursor in NO production. This suppressed both tau phosphorylation and the learning and memory deficits. In addition, elevated p-tau in eNOS knockouts could not be boosted further by high salt, supporting the idea that suppression of endothelial NO was behind the tau modification.

Delving more deeply into the mechanism, Faraco found that the salty food elevated calpain activity in the brain. Calpain cleaves p35 to p25; in keeping with this, the levels of the smaller peptide rose, as did activity of Cdk5, the tau kinase. All told, the data suggest that by triggering IL-17 production in the gut, high salt triggers loss of endothelial NO, which in turn leads to phosphorylation of tau and cognitive impairment.

Precisely how NO is suppressed remains to be seen. Katusic emphasized that the gas easily diffuses. Since cells in the brain are rarely more than 15 micrometers away from a blood vessel, NO could be an important signaling molecule. Faraco found no gross changes in astrocytes, microglia, or neurons in mice on high salt, as judged by GFAP, Iba1, and NeuN staining, but agreed it would be important to study downstream effects on these cells.

In her SfN talk, Austin reported that NO affected on microglia more profoundly. In cultures of the cells from eNOS knockout mice, she found not only an increase in ADAM17, but also decrease in cell surface TREM2. Mutations in this microglial receptor increase risk for Alzheimers and frontotemporal dementia. The sensor plays a central role in microglial homeostasis (Nov 2012 news; Oct 2012 news; Aug 2019 news). Austin also found that eNOS-/- microglia, either cultured or isolated from brain by cell sorting, make less TNF and IL-10, pro- and anti-inflammatory cytokines, respectively, while at the same time ramping up phospholipase A2, which mobilizes arachidonic acid, a precursor for inflammatory molecules.

We are slowly developing this concept that vascular mechanisms independent of perfusion affect cognitive impairment, said Katusic. Tsai and Blanchard agreed. Further unraveling these mechanisms will undoubtedly be a promising endeavor that will strengthen our understanding of how dietary habits influence susceptibility to age-related cognitive decline, they wrote.

For his part, Faraco is using RNA-Seq to study what happens in the endothelial cells to reduce NO. It will be interesting to examine interactions with other genetic and dietary risk factors, such as high-fructose or high-fat diets, he said. He thinks it will be important to identify the tau species responsible for the effects on cognition. We need to go much more deeply into the mechanism of neuronal dysfunction.Tom Fagan

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Not Just Blood PressureDietary Salt Linked to Tau Phosphorylation - Alzforum