The Trouble with Iron: Part IV The Nitty Gritty of What Happens in Your Brain!


References: The MindSpan Diet, Nature Communications, Front Aging Neurosci, Maynard: Jr Biological Chem, Annual Review of Neurosci,

Bear with me. I need to know the details of just what happens in your brain that makes iron so destructive. So here goes. You can get a wonderful synopsis by reading the MindSpan Diet book, or if you want a deep dive, I’ve got links here to some of the most meaningful literature.

For starters, what is the role of the APOe -4 gene? Having one copy doubles your risk of Alzheimer’s (AD), but two copies is a 10 times risk. Only 2% of Americans have two copies, but they are 15% of AD. Just two years ago, the AD Neuroimaging Initiative published a very strong paper showing that the APOe gene drives iron into the brain, and the level of iron in the brain, (as measured by cerebrospinal fluid ferritin) correlated with cognitive decline.

Along comes gene number 2, the APP gene. It was found in Down’s folks, who inevitably get dementia, and who have 3 copies of the APP gene. (It’s on chromosome 21 which Down’s folks have 3 copies of instead of two.)

Now, here is the key. We have 20,000 genes. Only 20 of them are responsive to levels of iron in our environment. It’s called the Iron-Response Element. It gets turned on when there is more iron, turning on the production of the APP protein. APP protein has the job of exporting the extra iron out of the brain.

The importance and centrality of the IRE system and the APP gene comes from population research in Iceland. There, a small and homogenous population allows genetic research to flourish. There are Icelandic folks who have a genetic variation of the APP gene, and they get about 10 years of brain protection out of it. Or, they have a 7.5 times less likely to get AD at age 85 than the rest of Icelanders. Lucky devils. It completely negates the danger of the APOe-4 gene. That really fingers the APP system as being in the forefront of causing AD. There it is.

So, let’s just simplify the sequence.

1.   You have too much iron, either because you ate too much red meat, took too many iron pills, or had two copies of the APO-e 4 gene. (Bad luck or bad environment.)

2.  The IRE system turns on, like your sprinkler system in your building in response to a fire.

3.   The production of APP protein turns on. (The sprinklers are blasting water everywhere, trying to douse the flame of too much iron.)

4.  The brain equivalent of Servrpro comes along to clean up the mess and ends up clipping a piece off the APP protein that gets left behind. That piece ends up accumulating in plaques, called beta-amyloid.

5.   As amyloid pieces accumulate, the clean up crew has to work overtime, using up its ability to duplicate  (the cells can only duplicate themselves so many times, each time shortening their telomeres and finally being unable to clean up at all).  Clean up slows.

6.  AD accelerates and the brain falls apart.  You slow.

Well, you can’t control your genes. You got what you got. You also can’t control the other elements of the breakdown process. But you can control your iron. That’s what is in your power.

WWW.What will work for me. It’s all about lowering your ferritin. What we haven’t talked about yet is the roll of copper. That may be as bad as iron, and that is coming next week. For now, I’m thinking about how to get rid of my iron. I’ve got too much and I now have the supplies in my office to do “phlebotomy” – cleaning and carefully draining blood out of you. If you can’t give it to the blood donation center. Please, please, please, do that first. Remember – you are aiming for a ferritin of 40. Give yourself a year to get there. Each time you give blood, your ferritin will drop about 20-40 points.

Pop Quiz

  1.   The APP protein is responsible to get extra iron out of your brain? T or F              Answer: True

2.     The Iron Responsive Element is one of 20 proteins in our genome that turns on in response to too much iron, and it turns on the production of more APP? T or F                             Answer: In a nutshell, you got it

3.   Your iron level in your spinal fluid reflects what’s in your brain. T or F                      Answer: Right again. True

4.   Blood donation will lower your ferritin. T or F                                                                 Answer; True. Isn’t that just too easy?

5.   We have tried our best to make sure people have enough iron. That is good for…..?                   Answer: Young menstruating women. Not so good for those of us over age 50.

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