Study Shows Direct Relationship Between Alzheimer’s Tau Protein and Cholesterol

We have known for some years that Alzheimer’s disease is characterised by two types of lesions, amyloid plaques and degenerated tau protein. Cholesterol plays an important role in the physiopathology of this disease. Two French research teams (Inserm/CEA/University of Lille/University of Paris-Sud ) have just shown, in a rodent model, that overexpressing an enzyme that can eliminate excess cholesterol from the brain may have a beneficial action on the tau component of the disease, and completely correct it. This is the first time that a direct relationship has been shown between the tau component of Alzheimer’s disease and cholesterol. This work is published in the 10 September 2015 issue of Human Molecular Genetics.

Original Research: Abstract for “CYP46A1 inhibition, brain cholesterol accumulation and neurodegeneration pave the way for Alzheimer’s disease” by Fathia Djelti, Jerome Braudeau, Eloise Hudry, Marc Dhenain, Jennifer Varin, Ivan Bièche, Catherine Marquer, Farah Chali, Sophie Ayciriex, Nicolas Auzeil, Sandro Alves, Dominique Langui, Marie-Claude Potier, Olivier Laprevote, Michel Vidaud, Charles Duyckaerts, Richard Miles, Patrick Aubourg, and Nathalie Cartier in Brain. Published online July 3 2015 doi:10.1093/brain/awv166

Overexpressing an enzyme that can eliminate excess cholesterol from the brain may have a beneficial action on the tau component of the disease, and completely correct it. Image is for illustrative purposes only. Credit: NIA/NIH.

anonymous asked:

Is there really no way to reverse arterial plaque buildup? Even with lifestyle changes, you're stuck with whatever plaque you had?

It’s not impossible to decrease arterial cholesterol plaques, but for most patients, it’s very difficult. Most pharmacologic treatments are aimed at slowing or stopping plaque progression and at stabilizing current plaques. When arteries narrow slowly, the heart generally grows new ones around it so blood supply doesn’t suffer. Most heart attacks come when plaques in arteries rupture. Then a blood clot builds around the rupture spot and blocks blood flow acutely. 

So if we stabilize the clots and prevent them from getting bigger, we can prevent heart attacks.

But back to shrinking plaques: that comes from pretty radical lifestyle changes in most peoples’ cases. Exercise and high dietary (not supplemental) fiber intake will both lower bad cholesterol levels. And we’ve learned that fat isn’t necessarily a bad thing when it comes to heart health. Studies have shown that saturated fat from whole foods (like dairy and unprocessed meats) decreases risk of cardiovascular disease, whereas saturated fat intake from processed foods increases it. Overall, the Mediterranean diet, which is full of omega-3 fats and “good” carbs has been shown to be the best for decreasing cardiovascular events and cardiovascular deaths. So yeah, with strenuous lifestyle change, damage can be reversed. But remember that the best option is preventing plaques from starting by living a healthy lifestyle early on.


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(Image caption: Fluorescent labelling of the Tau protein in a hNT human cell. Credit: © Inserm / U837)

Modulation of brain cholesterol: a new line of research in Alzheimer’s disease treatment?

We have known for some years that Alzheimer’s disease is characterised by two types of lesions, amyloid plaques and degenerated tau protein. Cholesterol plays an important role in the physiopathology of this disease. Two French research teams (Inserm/CEA/University of Lille/University of Paris-Sud) have just shown, in a rodent model, that overexpressing an enzyme that can eliminate excess cholesterol from the brain may have a beneficial action on the tau component of the disease, and completely correct it. This is the first time that a direct relationship has been shown between the tau component of Alzheimer’s disease and cholesterol. This work is published in the 10 September 2015 issue of Human Molecular Genetics.

Excess brain cholesterol cannot freely cross the blood-brain barrier; to be eliminated it must be converted into 24-hydroxycholesterol (24-OHC) by the enzyme CYP46A1 (cholesterol-24-hydroxylase). At Inserm Unit 1169, Nathalie, Cartier, coordinator of this work, and Patrick Aubourg, director of the unit, proposed the hypothesis that increasing the efflux of cholesterol from the brain by overexpressing CYP46A1 might have a beneficial effect on the elements of Alzheimer pathology.

The first step in this work made it possible to show that injecting a viral vector, AAV-CYP46A1, effectively corrects a mouse model of amyloid pathology of the disease, the APP23 mouse. CYP46A1 thus appears to be a therapeutic target for Alzheimer’s disease.

Conversely, in vivo inhibition of CYP46A1 in the mice, using antisense RNA molecules delivered by an AAV vector administered to the hippocampus, induces an increase in the production of Aß peptides, abnormal tau protein, neuronal death and hippocampal atrophy, leading to memory problems. Together these elements reproduce a phenotype mimicking Alzheimer’s disease.

These results demonstrate the key role of cholesterol in the disease, and confirm the relevance of CYP46A1 as a potential therapeutic target (work published in Brain on 3 July 2015).

Taken together, this work now enables the research team coordinated by Nathalie Cartier, Inserm Research Director, to propose a gene therapy approach for Alzheimer’s disease: intracerebral administration of a vector, AAV-CYP46A1, in patients with early and severe forms (1% of patients, familial forms) for whom there is no available treatment.

“To achieve this objective, we are carrying out all the preclinical steps of development and validation of the tools (vector, neurosurgical protocol, elements of monitoring) for demonstrating the efficacy and tolerance of the strategy, in order to submit an application for authorisation of a clinical trial,” explains Nathalie Cartier.



Today is the birthday of Konrad Emil Bloch, a German-American scientist who fled Nazi Germany in 1936.  Born January 21, 1912 in Neisse, Bloch began his studies at the Technical University of Munich.  Upon his arrival in the United States, he finished his Ph. D at Columbia University, where he taught for several years.  He was also a prolific and original writer.  In 1994 he published  Blondes in Venetian Paintings, the Nine-Banded Armadillo, and Other Essays in Biochemistry, an unusual look at science and biochemistry in particular.  

His career included the very best universities in the US:  Columbia, Harvard, University of Chicago.  His main contribution to science and the reason for his Nobel Prize in 1964 was his discovery of the mechanisms of cholesterol production in the body.  The word was coined in 1827 in French as cholestrine and entered English in 1894 with new suffix -ol to denote an alcohol base.  A combination of the Ancient Greek words khole meaning bile and steros meaning stiff or solid.  The solid part of the nomenclature came from gallstones:  cholesterol was originally separated and identified in the gallstones in solid form.  

Image of cholesterol Crystals in Synovial Fluid (compensated polariscopy) by Ed Uthman under Creative Commons 3.0 license.  Image of Konrad Bloch courtesy Nobel Media.

openemptythoughts  asked:

I know this isn't NECESSARILY a fat-related question, but more so a "I don't trust mainstream health politics" question, but: what do you know about the correlations between cholesterol levels and heart attack / heart health? I've heard some things that recently people are more skeptical of the direct relationship, and also that those with genetically high cholesterol are not able to lower it with any diet changes. Thoughts / a direction to look for answers?

It is well established that fatness is correlated with higher blood lipid levels (cholesterol/triglycerides), and that blood lipid levels is in turn correlated with cardiovascular disease. Based on this correlation, dietary changes and “maintaining a healthy weight” are often recommended to lower the risk of heart disease. 

But what does the science tell us?

One meta-analysis concluded that “Increasing soluble fiber can make only a small contribution to dietary therapy to lower cholesterol”. 

Another meta-analysis found that: “compliance with current dietary recommendations (30% of energy from fat, < 10% from saturated fat, and < 300 mg cholesterol/d) will reduce plasma total and low-density-lipoprotein-cholesterol concentrations by approximately 5% compared with amounts associated with the average American diet.” 

Exercise also appears to lower cholesterol by a similarly small margin. 

Regarding the potential benefits of weight loss, a recent meta-analysis of weight-loss experiments that included long-term follow-up of participants found that diet/exercise/weight loss did not lower blood lipid levels in any meaningful way (i.e., less than 0.25 mmol/L change), these small observed changes were not correlated with weight loss, and weight-loss did not predict a decreased incidence of cardiovascular disease.

Furthermore: “A meta-analysis of prospective epidemiologic studies showed that there is no significant evidence for concluding that dietary saturated fat is associated with an increased risk of CHD or CVD.”

Based on these results, it seems like changes in diet, exercise, and weight-loss have negligible effects on blood lipid levels, and similar (non) effects on incidence of cardiovascular disease. I’m not sure what to make of these results, but as with all things fat and health related, it seems that the literature poses more questions than answers.

-  Mod D

Do Statins Produce Neurological Effects?

Statins can indeed produce neurological effects. These drugs are typically prescribed to lower cholesterol and thereby reduce the risk of heart attack and stroke. Between 2003 and 2012 roughly one in four Americans aged 40 and older were taking a cholesterol-lowering medication, according to the Centers for Disease Control and Prevention. But studies show that statins can influence our sleep and behavior—and perhaps even change the course of neurodegenerative conditions, including dementia.

The most common adverse effects include muscle symptoms, fatigue and cognitive problems. A smaller proportion of patients report peripheral neuropathy—burning, numbness or tingling in their extremities—poor sleep, and greater irritability and aggression

Interestingly, statins can produce very different outcomes in different patients, depending on an individual’s medical history, the statin and the dose.
Cholesterol Other Factor
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anonymous asked:

Why do so many people these days think cholesterol is good for you? Even my parents think this now. It's driving me crazy!!

Hey anon,

I think the confusion comes from the fact that cholesterol is not by itself a bad thing, it provides an essential function. The thing is though, our body produces enough cholesterol by itself. Additional cholesterol we take in through animal products is automatically “bad cholesterol” and is harmful to our health, the higher your blood cholesterol level, the greater your risk for developing heart disease or having a heart attack, which is the number one killer of both men and women in the U.S. Interestingly, when it comes to the whole “we’re supposed to eat meat” thing, we are the only meat eaters on earth whose arteries get clogged when we consume animal protein. 

People take expensive cholesterol combating medicine or even surgery to combat high cholesterol, but the good news is that a plant based diet is all you need to avoid the problem completely. While vegans can of course get heart disease too (though we do enjoy a much chance of developing it), the only significant sources of cholesterol are animal products, so as vegans we never have to worry about this major health risk. The fact that many health professionals will offer expensive pils before recommending a plant based diet should tell you more than you need to know about the ignorance of most health professionals when it comes to plant based nutrition.
The Truth About Cholesterol, Statin Drugs, and Cancer
25 million Americans are on statin drugs to lower cholesterol and decrease their chance of heart disease. Discover how they may be causing cancer instead.

Cholesterol Drugs Increase Risk of Cancer and Death

Cholesterol drugs, as revealed in a 1993 study published in the Journal of the American Medical Association, have been causally associated with an increased risk of non-cardiovascular health conditions. These are essentially any disease not related to the heart or blood vessels, as well and death. A team of researchers from the University of California, San Francisco (UCSF) determined that the intervention-based method of using fibrates and/or statins to lower cholesterol may be a misguided one that’s putting millions of people at risk.

What they found is that patients who lower their cholesterol levels by taking such drugs simultaneously increase their risk of developing other chronic health conditions such as cancer. This is significant because it reiterates the fact that lowering cholesterol with drugs isn’t the catch-call for increasing mortality that the medical system often claims it is. It also supports the notion that high cholesterol itself isn’t necessarily even a problem.

“Meta-analyses of primary prevention trials in middle-aged men reveal an increase in non-CHD (coronary heart disease) deaths among those randomized to cholesterol interventions, an unexpected finding that is more substantial than the decrease in CHD deaths,” the authors reported.

“This raises the possibility that one or more of the cholesterol interventions could have very serious adverse effects among young adults, whose risk of non-CHD death is normally 100 times their risk of CHD death.”
Eggs Don't Cause Heart Attacks -- Sugar Does
It's over. The debate is settled. It's sugar, not fat, that causes heart attacks. Oops. Fifty years of doctors' advice and government eati...

It’s over. The debate is settled.

It’s sugar, not fat, that causes heart attacks.

Oops. Fifty years of doctors’ advice and government eating guidelines have been wrong. We’ve been told to swap eggs for cereal. But that recommendation is dead wrong. In fact, it’s very likely that this bad advice has killed millions of Americans.

A rigorously done new study shows that those with the highest sugar intake had a four-fold increase in their risk of heart attacks compared to those with the lowest intakes. That’s 400 percent! Just one 20-ounce soda increases your risk of a heart attack by about 30 percent.

This study of more than 40,000 people, published in JAMA Internal Medicine, accounted for all other potential risk factors including total calories, overall diet quality, smoking, cholesterol, high blood pressure, obesity and alcohol.

This follows on the heels of decades of research that has been mostly ignored by the medical establishment and policy makers. In fact, the Institute of Medicine recommends getting no more than 25 percent of your total calories from added sugar. Really? This study showed that your risk of heart attacks doubles if sugar makes up 20 percent of your calories.

Yet more than 70 percent of Americans consume 10 percent of their daily calories from sugar. And about 10 percent of Americans consume one in every four of their calories from sugar.

Failed Dietary Guidelines

U.S. Dietary Guidelines provide no limit for added sugar, and the U.S. Food and Drug Administration (FDA) still lists sugar as a “generally regarded as safe” (GRAS) substance. That classification lets the food industry add unlimited amounts of sugar to our food. At least the American Heart Association recommends that our daily diet contain no more than 5 percent to 7.5 percent added sugar. Yet most of us are eating a lot more. Most of us don’t know that a serving of tomato sauce has more sugar than a serving of Oreo cookies, or that fruit yogurt has more sugar than a Coke, or that most breakfast cereals — even those made with whole grain — are 75 percent sugar. That’s not breakfast, it’s dessert!

This is a major paradigm shift. For years, we’ve been brainwashed into thinking that fat causes heart attacks and raises cholesterol, and that sugar is harmless except as a source of empty calories. They are not empty calories. As it turns out, sugar calories are deadly calories. Sugar causes heart attacks, obesity, Type 2 diabetes, cancer and dementia, and is the leading cause of liver failure in America.

The biggest culprit is sugar-sweetened beverages, including sodas, juices, sports drinks, teas and coffees. They are by far the single biggest source of sugar calories in our diet. In fact, more than 37 percent of our sugar calories come from soda. The average teenage boy consumes 34 teaspoons of sugar a day, or about 544 calories from sugar. Even more troubling, this isn’t just putting kids at risk for heart attacksat some remote later date in their lives. It’s killing them before their 20th birthday.

This new research syncs with decades of data on how sugar causes insulin resistance, high triglycerides, lower HDL (good) cholesterol and dangerous small LDL (bad) cholesterol. It also triggers the inflammation we now know is at the root of heart disease.

And fats, including saturated fats, have been unfairly blamed. With the exception of trans fats, fats are actually protective. This includes omega-3 fats, nuts and olive oil, which was proven to reduce heart attack risk by more than 30 percent in a recent large randomized controlled study.

Here’s the simple fact: Sugar calories are worse than other calories. All calories are not created equal. A recent study of more than 175 countries found that increasing overall calories didn’t increase the risk of Type 2 diabetes, but increasing sugar calories did — dramatically.

How to Cure Our Sugar Addiction

America lags far behind the rest of the world in addressing this problem. Mexico, for example, responded after learning that when soda consumption increased to 20 percent of calories for the average citizen, their rates of obesity and Type 2 diabetes skyrocketed. Public health officials there researched effective solutions to combat obesity and diabetes from around the world.

The key interventions they implemented included taxing soda, banning junk food television advertising, and eliminating processed foods, junk food and sugar-sweetened beverages from schools. More than 15 countries have targeted sugar-sweetened beverages by taxing them — a strategy that’s proven successful.

Another effective strategy is revamping food labeling to make it clear if a food is good, should be consumed with caution, or is bad for you. In the United States, even someone with a Ph.D. in nutrition has trouble deciphering food labels. How can the average person be expected to know?

Recent and mounting scientific evidence clearly proves that sugar — and flour, which raises blood sugar even more than table sugar — is biologically addictive. In fact, it’s as much as eight times more addictive than cocaine.

The average American consumes about 152 pounds of sugar and 146 pounds of flour a year. It’s imperative that we revamp our outdated and dangerous national dietary guidelines. And we need clear strategies and medical programs to help people understand and address the health risks and addictive nature of sugar and refined carbohydrates.

That’s how we can reverse this tsunami of obesity and chronic disease that is robbing us of our health and crippling our economy.

Wishing you health and happiness,

Mark Hyman, MD

In my new book, The Blood Sugar Solution 10-Day Detox Diet, which will be released on February 25, I provide an easy, step-by-step plan to rid yourself of sugar addiction and reverse your risk of heart attacks. To download a sneak preview of this book, go to and pre-order the book on Amazon

Mark Hyman, MD is a practicing physician, founder of The UltraWellness Center, a six-time New York Times bestselling author, and an international leader in the field of Functional Medicine. You can follow him on Twitter, connect with him onLinkedIn, watch his videos on YouTube, become a fan on Facebook, and subscribe to his newsletter.

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If you’re a vegan, you don’t get any dietary cholesterol because cholesterol is only found in animal products. BUT… what if you go down on someone? Do you get cholesterol from that? I mean, whatever it is, it’s nutritious. I just really wonder if there is any cholesterol in your secretions.

Pls answer. Thanks.

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