Sugar's 'tipping point' link to Alzheimer's disease revealed

February 23, 2017
Professor Jean van den Elsen and Dr Omar Kassar in the laboratory. They have worked to reveal a molecular link between sugar and Alzheimer's Disease Credit: AP Commercial Photography

For the first time a "tipping point" molecular link between the blood sugar glucose and Alzheimer's disease has been established by scientists, who have shown that excess glucose damages a vital enzyme involved with inflammation response to the early stages of Alzheimer's.

Abnormally levels, or hyperglycaemia, is well-known as a characteristic of diabetes and obesity, but its link to Alzheimer's disease is less familiar.

Diabetes patients have an increased risk of developing Alzheimer's disease compared to healthy individuals. In Alzheimer's disease abnormal proteins aggregate to form plaques and tangles in the brain which progressively damage the brain and lead to severe cognitive decline.

Scientists already knew that glucose and its break-down products can damage proteins in cells via a reaction called glycation but the specific molecular link between glucose and Alzheimer's was not understood.

But now scientists from the University of Bath Departments of Biology and Biochemistry, Chemistry and Pharmacy and Pharmacology, working with colleagues at the Wolfson Centre for Age Related Diseases, King's College London, have unraveled that link.

By studying brain samples from people with and without Alzheimer's using a sensitive technique to detect glycation, the team discovered that in the early stages of Alzheimer's glycation damages an enzyme called MIF (macrophage migration inhibitory factor) which plays a role in immune response and insulin regulation.

MIF is involved in the response of brain cells called glia to the build-up of abnormal proteins in the brain during Alzheimer's disease, and the researchers believe that inhibition and reduction of MIF activity caused by glycation could be the 'tipping point' in disease progression. It appears that as Alzheimer's progresses, glycation of these enzymes increases.

The study is published in the journal Scientific Reports.

Professor Jean van den Elsen, from the University of Bath Department of Biology and Biochemistry, said: "We've shown that this enzyme is already modified by glucose in the brains of individuals at the early stages of Alzheimer's disease. We are now investigating if we can detect similar changes in blood.

"Normally MIF would be part of the to the build-up of abnormal proteins in the brain, and we think that because sugar damage reduces some MIF functions and completely inhibits others that this could be a tipping point that allows Alzheimer's to develop.

Dr Rob Williams, also from the Department of Biology and Biochemistry, added: "Knowing this will be vital to developing a chronology of how Alzheimer's progresses and we hope will help us identify those at risk of Alzheimer's and lead to new treatments or ways to prevent the disease.

Dr Omar Kassaar, from the University of Bath, added: "Excess sugar is well known to be bad for us when it comes to diabetes and obesity, but this potential link with Alzheimer's disease is yet another reason that we should be controlling our sugar intake in our diets."

Globally there are around 50 million people with Alzheimer's disease, and this figure is predicted to rise to more than 125 million by 2050. The global social cost of the disease runs into the hundreds of billions of dollars as alongside medical care patients require social care because of the cognitive effects of the disease.

The study was funded by the Dunhill Medical Trust. Human brain tissue for this study was provided through Brains for Dementia Research, a joint initiative between Alzheimer's Society and Alzheimer's Research UK in association with the Medical Research Council.

Explore further: Alzheimer's researchers investigate diabetes link in mice

More information: Omar Kassaar et al, Macrophage Migration Inhibitory Factor is subjected to glucose modification and oxidation in Alzheimer's Disease, Scientific Reports (2017). DOI: 10.1038/srep42874

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baudrunner
not rated yet Feb 23, 2017
I think that a person needs to be a specific phenotype for linking hyperglycemia to Alzheimer's. I have know several people who were essentially sugar addicts - candy, pastry, cookies, cakes, you name it - who lived much longer than average lives and never developed neuro-degeneration.

Long lineages of the well-to-do probably fit this type, whereas those descended from the lower working classes, who would not historically have had the resources to develop a sweet tooth, might be more susceptible.
rrrander
not rated yet Feb 23, 2017
This lunatic crusade against sugar has ZERO basis in fact. People ate FAR more sugar decades ago, yet alzheimers is now manifesting itself in people who didn't all live that far back. In addition, curtailing the consumption of sugar by "social engineering" (force) will not reduce obesity. Sugar is highly satisfying, unlike other foods and this prevents overconsumption of calories. In the past, when people did things like eating desert after a meal, or had a sugared drink during the meal, people WERE NOT NEARLY AS FAT on average as today. People, young people will simply eat more of other things in order to get the same level of satisfaction and will end-up consuming far too many calories and obesity will rise, along with T-2 diabetes.
aswheeler77
not rated yet Feb 24, 2017
Bacteria is probably the biggest culprit. Refined carbs (Including "free sugars", not fruit sugars locked away inside the fibrous matrix of a whole fruit.) and grain consumption seems to be biggest culprit behind bacteria. Gluten grains for its own special reasons (Gliadin binds to the CXCR3 receptor which is normally used by the body to widen the epithelial junction gaps in the intestinal lining for T-Cell passage, which allows staph aurues and other small bacteria entry to the blood stream it didn't have before.). The link between bacteria and blood sugar is this -> bacteria invades -> immune system activates -> Cortisol is released to control/regulate the immune reponse -> Cortisol causes vasoconstriction, increased blood pressure and increased blood sugar levels.
weaser200
not rated yet Feb 24, 2017
Lack of insulin causes Alzheimers, but Coconut oil will help increase your insulin, if you have a natural surplus of insulin, you will not be affected by too much sugar, up to a limit, but yet over time, too much sugar will cause cancer. Another condition that is confused with Alzheimers, is Cloudy Memory, for that you can take Turmeric to reduce the Aluminum in the brain, Aluminum is often found in pasteries & bread associated with self rising flour. The natural treatment for Cancer is Tomatoes & Greens, my wife prefers Vegetable juice, it is more convenient.
aswheeler77
not rated yet Feb 24, 2017
@Weaser - Coconut oil and Turmeric are both strongly antibacterial. More support for the bacterial hypothesis. I wonder how French alzheimer rates compare to Germany's? They are definitely more germ-phobic in their diet, and they have half the heart attack and stroke rates. Suspect there's a similar trend in Alzheimers.
aswheeler77
not rated yet Feb 24, 2017
Well, seems like they have comparable alzheimers rates according to alzheimer's europe dot org. Not a particularly strong argument against the bacterial hypothesis, since they both consume wheat, but not a particularly strong one for.
weaser200
not rated yet Feb 24, 2017
aswheeler77 , bacteria has little to do with this, they do not destroy the normal stomach bacteria that digest the foods, but antibiotic & sugar will destroy the stomach bacteria, then you will need Acidophillus to replace the stomach bacteria, if you are worried about Cholesterol or Heart disease, try a teaspoon of vinegar in a glass of water each day. People that eat less sugar are less likely to suffer lack of insulin, which is the cause of Alzheimers Disease.
aswheeler77
not rated yet Feb 24, 2017
Vinegar is another strong antibacterial. In regard to your sugar being antibacterial, it's true that sucrose will inhibit bacteria, but after the amylase in the mouth/throat/stomach/small-intestine splits the sucrose into their fructose/glucose molecules before absorption, bacteria has a field day off it, so no, free sugars are DEFINITELY NOT antibacterial. Especially since refined sugars get QUICKLY converted into their fructose and glucose molecules.

Anyway... should I list off all the antibacterial foods I know of... the list is rather extensive...
drpoundsign
not rated yet Feb 24, 2017
I'm a Physician. To Me, this article emphasizes the futility of Drugs against Amyloid and Tau-almost as worthless as Aricept. Those who saw "Concussion" know what the Brains of football players like Mike Webster looked like. The Brains of Alzheimer's patients are full of Fungus. They also have certain viruses that a normal brain does not. Giving relatively nontoxic drugs like Diflucan would make sense in early Cognitive Impairment. And, YES, I DO believe in the sugar link. The Mediterranean and Norwegian diets both protect the Brain. Lots of fish, with fruits and vegetables and limit sugar. A few cups of Green Tea/day is probably also very helpful. The Okinawa Japanese live long lives with their brains intact. The Chinese who do make it into their nineties, are similarly in relatively Good shape mentally.
aswheeler77
not rated yet Feb 24, 2017
Okay, so I'm going to take another approach. Is there an association between alzheimers and the known bacteria caused problems, like heart disease, liver disease and dementia?

From https://www.ncbi....16918818

"Growing evidence supports a strong and likely causal association between cardiovascular disease (CVD), and its risk factors, with incidence of cognitive decline and Alzheimer's disease. Individuals with subclinical CVD are at higher risk for dementia and Alzheimer's. Several cardiovascular risk factors are also risk factors for dementia, including hypertension, high LDL cholesterol, low HDL cholesterol and especially diabetes."

They didn't quantify the association, but a "strong association" suggests a strong role bacteria plays in the disease. In particular, staph aureus and protein A which appears to coat Von Willebrand factor surfaces and clog up associated vessels, and it appears that VWF is associated with the brain.
aswheeler77
not rated yet Feb 24, 2017
On VWF and the brain...

https://www.ncbi....23825365

"Endothelial Von Willebrand factor promotes blood-brain barrier flexibility and provides protection from hypoxia and seizures in mice."

"Aberrant blood-brain barrier (BBB) permeability is a hallmark pathology of many central nervous system diseases. von Willebrand factor (VWF) is stored in endothelial Weibel-Palade bodies from where it is released on activation into plasma and basement membrane."

It appears that the reduced endothelial flexibility and "clogging up" that Staph Aureus's Protein A has may induce hypoxia to the brain, inducing disease/death states in the brain, like that of Alzheimers.
aswheeler77
not rated yet Feb 24, 2017
Anyway, I'm going to post the current list of antibacterial foods here that I have.

fruit skins, omega 3 fatty acids, flaxseeds, flax oil, fish oil, fish skin, garlic, turmeric, coconut oil, cocoa, coffee, lemons, limes, grapefruits, vinegar, red wine (Probably due to the essence of red grape skins), hops, that one bitter chinese herb, egg whites, penicullum mold variants (Such as penicillium roqueforti commonly found in blue cheese), various herbs.

Others with unknown or weaker antibacterial properties (Bacteriostatic).

Nuts, cinnamon, salt, grass fed fermented cow products(substantially higher omega 3 fat content) [cheese, sour cream, butter].
aswheeler77
not rated yet Feb 24, 2017
And, to make the connection between hypoxia and alzheimers, here's a paper on it.

https://www.ncbi....17705799

"However, emerging evidence suggests that pathological cellular remodelling caused by chronic hypoxia shows striking similarities to those observed in the central nervous system as a consequence of AD. Furthermore, prolonged hypoxia can induce formation of Abetas (amyloid beta peptides), the primary neurotoxic elements of AD, which accumulate over years to form the extracellular plaques that are the hallmark feature of the disease. Hypoxia can lead to paradoxical increases in mitochondrial ROS (reactive oxygen species) generation upstream of Abeta formation."

So, diet->staph aureus's protein A -> reduced endothelial flexibility in the vwf surfaces in the blood-brain barrier and increased bloodflow obstruction from the plaques -> prolonged brain hypoxia -> abeta formation

That's the bacteria link.
aswheeler77
not rated yet Feb 24, 2017
To prevent alzheimers, I would suggest.

1) Regular exercise (Expands the arteries)
2) Minimal consumption of refined carbs and grains, especially gluten grains.
3) Regular social activity (Bonding being key here, oxytocin counteracts the effects of cortisol.). Staying relaxed (being in relaxing environments, like being on a tropical island, lol), etc.
4) Regular consumption of blood flow promoters, like nitrate-rich foods(spinach, green leafy vegetables,etc.), lycopene rich foods (Tomatos, watermelons, sweet potatos, papayas, etc.) and beta-carotene rich foods (Carrots,sweet potatos,etc.).
5) Regular consumption of antibacterial foods (list in an above post.)

If one is at lost for carb sources, there's two great sources of carbs. Whole fruits and high fiber vegetable starches like cassava and sweet potatos. (Ideally prepared with methods that keep the fiber intact, like boiling and other low temperature methods.)
papuebiswas
not rated yet Mar 13, 2017
This story is very interesting as it relates to a few of the trends that we are seeing in the healthcare arena. Chronic diseases are the leading cause of the death in the U.S.; this further justifies why we should push for a shift to more patient-centered care.

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