Amyloid Precusor Protein - The Raw Material for the Amyloid Plaques in Alzheimer's Disease
"If you look at any risk factor for cardiovascular disease - the standard risk factors like high cholesterol, diabetes, hypertension, smoking, sedentary lifestyle, aging - all of these have been associated with loss of nitric oxide in the endothelium (the linings of blood vessels), a condition known as endothelial dysfunction."
-Zvonimir S. Katusic, M.D., Ph.D., senior author and professor at the Mayo Clinic, "Endothelial Nitric Oxide Modulates Expression and Processing of Amyloid Precursor Protein," Circulation Research published online ahead of print Dec. 2, 2010.-
"Once you lose that [baseline of] nitric oxide, you see the increases in APP (amyloid precursor protein) and BACE1 (an enzyme that together with APP helps to create Alzheimer plaques), and the increase in amyloid beta generation."
-Susan Austin, PhD., first author of the study, and a research fellow at the Mayo Clinic-
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This just might turn out to be the most important medical story of the year. Really! The puzzle pieces about the connection between cardiovascular health & Alzheimer's/dementia are finally starting to fit together. Click here for the American Heart Association press release. Click here for the article. Click here for the editorial.
Look, you know it's an important story when it appears in a major medical journal like Circulation Research, it has an accompanying editorial, and Heartwire publishes a press release about it.
For years we've been hearing that there is a connection between heart health and brain health. "What's good for the heart is good for the brain"--namely, don't smoke, get lots of exercise, eat lots of beans & green leafy vegetables, and cut out the fat.
Cardiovascular diseases and Alzheimer/brain diseases share similar blood vessel pathologies, but as Dr. Randolph Schiffer, the head of the Cleveland Clinic's Ruvo Center for Brain Health said last May, "We lack the exact kind of science we'd like to have concerning this connection."
Thanks to three researchers at the Mayo Clinic (Susan A. Austin, Ph.D., Anantha V. Santhanam, Ph.D., & Zvonimir S. Katusic, MD, Ph.D.) we may finally have that connection between heart & brain health: Nitric Oxide.
Here's why I'm so excited. If the loss of nitric oxide in the blood vessels of the brain is the culprit behind Alzheimer's & dementia, we've got a fixable problem. But, here's the catch. You can't wait too long to start fixing this problem. And, you have to be willing to change your lifestyle.
That means: Ditch the fat, now! Eat plant-based, now! Get off the couch, now! If you wait until your baseline nitric oxide supply gets too low, it may be too late.
- Preserving healthy blood vessel walls is important to preventing cognitive impairment and ultimately Alzheimer’s disease. And a hefty supply of nitric oxide is the key.
- As Dr. Caldwell Esselstyn has shown with hundreds of heart disease patients, you can preserve or repair your blood vessel walls by eating a plant-based diet that's high in the building blocks of nitric oxide: leafy greens, legumes, oats & beans.
- Exercise also stimulates the endothelium (blood vessel linings) to produce more nitric oxide.
- According to Esselstyn's research, just 3-4 weeks on a plant-based diet that's high in greens, without meat, dairy, added fat or oil, is all it takes to start the healing process in (coronary) blood vessels, and put the nitric oxide factory back into business. Let's hope it's true for the blood vessels in the brain, as well.
How Nitric Oxide Affects the Brain & Alzheimer's Disease
What are the hallmarks of Alzheimer's Disease?
The dread amyloid plaques & tangles. Neurofibrillary tangles, are the twisted fibers composed primarily of a protein called tau that arises inside nerve cells, or neurons; and amyloid plaques, which are the buildup between neurons of protein fragments, called amyloid beta peptides.
How did the Mayo Clinic researchers discover the connection between nitric oxide & Alzheimer's Disease?
First they tested out their theory using endothelial cells from the tiny blood vessels in the human brain. Here's where it gets a little technical, but stick with me. The scientists chemically stopped the production of eNOS (endothelial nitric oxide synthase), which is an enzyme that's responsible for producing nitric oxide.
Once, they stopped the production of nitric oxide in these endothelial cells, it triggered a series of biochemical effects that increased the production of a bad-boy protein, called: Amyloid precursor protein (APP). This is not a protein you want hanging around your brain's blood vessels. It's the raw material for the dread amyloid plaques that are seen in Alzheimer's patients.
And there's more. Once the nitric oxide supply was cut off, another bad-boy enzyme increased, and got real active: Beta-site amyloid precursor protein cleaving enzyme (BACE). This enzyme cleaves to APP & creates the amyloid beta peptides that make up Alzheimer plaques. Not a good situtation if you want prevent Alzheimer's.
But that's just in vitro research. Did the researchers test their discovery out in vivo--on animal models?
The researchers studied the tiny blood vessels in the brains of mice that had been genetically bred to lack the eNOS enzyme (endothelial nitric oxide synthase enzyme). That's the ezyme that's needed to produce nitric oxide. No eNOS enzyme means no NO (nitric oxide).
So, what happens when there's no eNOS ezyme to produce nitric oxide? It's not good. The mice had higher blood pressure and were prone to insulin resistance compared to normal mice--and they had about a 50% reduction in nitrites & nitrates which indirectly reflect nitric oxide production. Kind of like what happens to humans when their nitric oxide supply hits the skids. With a seriously hampered nitric oxide production, the mice brains showed higher levels of amyloid beta peptide, along with a lot more of those bad-boy amyloid plaque-makers, the APP & the BACE1. Which sounds like a recipe for Alzheimers.
So, what does this mean for our brains?
The study suggests that protecting the endothelial linings of the blood vessels of our brains is important to preventing cognitive impairment, and ultimately Alzheimer's Disease, according to Katusic, the lead researcher.
"On the cardiovascular side we've known for some time that preservation of healthy endothelium is critical to prevent major cardiovascular events. Now it seems this may have important implications for cognitive impairment."
Does this help to explain the cognitive benefit of exercise?
Katusic thinks so. Since exercise stimulates the endothelium to produce more nitric oxide, this research just might explain why aging exercisers have healthier brains, less cognitive impairment, and less Alzheimers than non-exercisers.
"There is a lot of literature showing that every time you exercise, you stimulate the endothelium to produce more nitric oxide. What we have identified in this paper may help explain the reported (cognitive) benefit of exercise." [Katusic]
Need more evidence for the link between exercise, heart health, and brain health? Check out: The Latest Framingham Heart Study. Brain Shrinkage? Atrophy of the Brain? Getting to the Heart of the Matter - It's All About the Cardiac Index
Nitric Oxide 101 - Protecting Your Nitric Oxide Supplier - The Endothelium
You aren't going to find the steady supply of nitric oxide you need for cardiovascular & brain health in a pill. You are going to have to produce your own supply, with your own endothelial cells.
And the only way you're going to get a direct & continous line of NO that will ensure that you keep your endothelial linings healthy is to do the heavy-lifting: diet & exercise.
"...it is clear to me that in achieving those [cholesterol-lowering] goals through plant-based nutrition, we also achieved a corollary result: we restored the body's own powerful capacity to resist and reverse vascular disease. Plant-based nutrition, it turns out, has a mighty beneficial effect on endothelial cells, those metabolic and biochemical dynamos that produce nitric oxide.
And, nitric oxide, as I have noted, is absolutely essential to vascular health--a finding that won the Nobel Prize for Medicine in 1998.
-Dr. Caldwell B. Esselstyn, Jr., Prevent and Reverse Heart Disease, pg. 41-42-
What impairs the supply of nitric oxide?
It's a Catch-22. Nitric oxide is diminished by all the usual suspects--the cardiovascular risk factors--like high cholesterol, high triglycerides, high homocysteine, high CRP (marker for inflammation), insulin resistance, high blood pressure, and smoking. These culprits impair the delicate endothelial cells' ability to produce ample nitric oxide.
What role does diet play in this endothelial cell/nitric oxide story?
Here's how Dr. Esselstyn explains it: "The basic understanding we all need to accept is that with every meal of oil, dairy, or meat we eat, within minutes there is damage & injury to the "life jackets" of our vascular health--which is the single layer of endothelial cells that line all of our blood vessels. The endothelial cells produce the "magical gas" called nitric oxide which keeps our blood vessels relaxed, prevents our white blood cells & platelets from becoming sticky, and prevents the growth of plaque--the dread "hardening of the arteries".
Is there anything we can eat to insure that our endothelial cells will have the raw materials to produce this healing nitric oxide?
Beans & leafy greens. Load up on kale, collards, Swiss chard, bok choy & beans and you will be well on your way to healing the linings of your blood vessels. Ditch the meat, dairy, & oil. And be sure to include a daily bowl of oatmeal while you're at it--with its nitric-oxide increasing avenanthramides. Click here to learn more.
Look, it's a win-win situation when it comes to boosting nitric oxide production. For certain you'll help your heart. And if the Mayo Clinic researchers are right, there's a good bet you'll prevent cognitive decline as well--or at least slow it down. And along the way, with the addition of a plant-based diet & exercise you're bound to lose weight, look great, get healthy, and feel fantastic.
NO (nitric oxide) is a YES YES! Just do it! NOW.