Skip to comments.Discovery supports theory of Alzheimer's disease as form of diabetes
Posted on 09/26/2007 10:02:14 AM PDT by Red Badger
Insulin, it turns out, may be as important for the mind as it is for the body. Research in the last few years has raised the possibility that Alzheimers memory loss could be due to a novel third form of diabetes.
Now scientists at Northwestern University have discovered why brain insulin signaling -- crucial for memory formation -- would stop working in Alzheimers disease. They have shown that a toxic protein found in the brains of individuals with Alzheimers removes insulin receptors from nerve cells, rendering those neurons insulin resistant. (The protein, known to attack memory-forming synapses, is called an ADDL for amyloid ß-derived diffusible ligand.)
With other research showing that levels of brain insulin and its related receptors are lower in individuals with Alzheimers disease, the Northwestern study sheds light on the emerging idea of Alzheimers being a type 3 diabetes.
The new findings, published online by the FASEB Journal, could help researchers determine which aspects of existing drugs now used to treat diabetic patients may protect neurons from ADDLs and improve insulin signaling in individuals with Alzheimers. (The FASEB Journal is a publication of the Federation of American Societies for Experimental Biology.)
In the brain, insulin and insulin receptors are vital to learning and memory. When insulin binds to a receptor at a synapse, it turns on a mechanism necessary for nerve cells to survive and memories to form. That Alzheimers disease may in part be caused by insulin resistance in the brain has scientists asking how that process gets initiated.
We found the binding of ADDLs to synapses somehow prevents insulin receptors from accumulating at the synapses where they are needed, said William L. Klein, professor of neurobiology and physiology in the Weinberg College of Arts and Sciences, who led the research team. Instead, they are piling up where they are made, in the cell body, near the nucleus. Insulin cannot reach receptors there. This finding is the first molecular evidence as to why nerve cells should become insulin resistant in Alzheimers disease.
ADDLS are small, soluble aggregated proteins. The clinical data strongly support a theory in which ADDLs accumulate at the beginning of Alzheimers disease and block memory function by a process predicted to be reversible.
In earlier research, Klein and colleagues found that ADDLs bind very specifically at synapses, initiating deterioration of synapse function and causing changes in synapse composition and shape. Now Klein and his team have shown that the molecules that make memories at synapses -- insulin receptors -- are being removed by ADDLs from the surface membrane of nerve cells.
We think this is a major factor in the memory deficiencies caused by ADDLs in Alzheimers brains, said Klein, a member of Northwesterns Cognitive Neurology and Alzheimer's Disease Center. Were dealing with a fundamental new connection between two fields, diabetes and Alzheimers disease, and the implication is for therapeutics. We want to find ways to make those insulin receptors themselves resistant to the impact of ADDLs. And that might not be so difficult.
Using mature cultures of hippocampal neurons, Klein and his team studied synapses that have been implicated in learning and memory mechanisms. The extremely differentiated neurons can be investigated at the molecular level. The researchers studied the synapses and their insulin receptors before and after ADDLs were introduced.
They discovered the toxic protein causes a rapid and significant loss of insulin receptors from the surface of neurons specifically on dendrites to which ADDLs are bound. ADDL binding clearly damages the trafficking of the insulin receptors, preventing them from getting to the synapses. The researchers measured the neuronal response to insulin and found that it was greatly inhibited by ADDLs.
In addition to finding that neurons with ADDL binding showed a virtual absence of insulin receptors on their dendrites, we also found that dendrites with an abundance of insulin receptors showed no ADDL binding, said co-author Fernanda G. De Felice, a visiting scientist from Federal University of Rio de Janeiro who is working in Kleins lab. These factors suggest that insulin resistance in the brains of those with Alzheimers is a response to ADDLs.
With proper research and development the drug arsenal for type 2 diabetes, in which individuals become insulin resistant, may be translated to Alzheimers treatment, said Klein. I think such drugs could supercede currently available Alzheimers drugs.
Source: Northwestern University
Beer is full of carbs unless you drink that pisswater Lite stuff!..............
Thanks for the suggestion. I do splurge every once in awhile even though my diet is actually very low carb, almost ketogenic due to a very strong genetic predisposition for metabolic syndrome. Even though I’m considered of moderate weight (5 7”, 135) I still have to be very careful. The diet maintains blood pressure, cholesterol and glucose levels all without drugs.
How about a recipe for low carb cheesecake! That sounds like a great thing to make.
PS- will try that beer.
True. I drink Yuengling Light (6.5g crabs) occasionally but most really tasty beers are high carb.
Actually it has carbs not “crabs”
Screw it. Here. Have a Twinkie.
I absolutely love German beers! Buy them every now and then locally. Some are called “liquid bread” in Germany they are so high in carbs!...............
I wonder if a very low carb diet would help with Parkinson’s. Does anyone know?
“...there is prevention. If it comes in a box or a bag, dont eat it. ... Reduce grain consumption to 20% of todays average human diet and most of these diseases will go away.”
You are on target. Add the elimination of polyunsaturated fats to the “don’t eat it” list and begin preventing heart disease, insulin resistance (diabetes), cancer, obesity, arthritis. None of these diseases were pandemic at the turn of the last century (100 years ago).
Replace grains with veggies; corn, soy, canola oils with coconut oil; margarine with butter. Eliminate sugar. Eliminate soft drinks. Eliminate artificial sweeteners. Eliminate cholesterol-lowering drugs (these can cause Alzheimer-like symptoms).
Unless the FDA continues to black label and ban those pharmacueticals that do the job best.
Troglitizone.....removed from the market.
Rosiglitizone (Avandia) .....black labeled.
Pioglitizone (Actos) ....the next one to go?
I realized that stuff was poison years ago, and stopped eating it years ago.
And sugar in my book includes corn syrup, cane juice, etc.
And I used to love that stuff.
My general rule is to be suspect of any substance that has to be cooked and/or undergo a lot of work to make it edible.
Because if it isn't theoretically edible "raw right off the tree or the hoof" it's probably not something we evolved to eat.
As an aside (so many here so knowledgeable) my husband has terrible problems with neuropathy in his lower and legs feet (it was pain and clumsiness that lead him to the doc in in the first place). Anybody taking any wonder drug that helps? When it acts up, he is literally up all night.
Don't panic. Actos works differently than Avandia and is so far not targeted for any action.
As for the neuropathy....his doc needs to assist. If there has been extensive nerve damage before he started getting treatment then it may be a problem for some time. So many variables. I have been on Actos and Metformin for some time but through diet and exercise have been able to get off of Glyburide (which whips the pancreas to produce more insulin) which can, over time, have a bad effect on the islet cells in the pancreas...making things worse.
That was one of my goals...to get off that drug.
There is a new product on the market that I have seen ads for that will combat the pain and burning in the legs and feet due to Type II...I don't recall the name but it is being advertised on TV these days.
If I find it I'll ping you.
For lunch I'm eating chicken preast or a 'burger patty with a salad. For dinner I have whatever the family is having minus the rice or potatoes. But breakfast *sucks*! I'm so sick of eggs that I want to puke. And veggies for breakfast...?! My tummy is not happy with that.
Benfotiamine may help your husband. It’s kept my type 1 diabetic son healthy so far!
We found out this year that many in my family have BeriBeri (thiamine or B1 deficiency) and we're now taking B1 shots.
The symptoms of BeriBeri are the same as the complications of diabetes. Benfotiamine is a synthetic B1 and is harder for the body to eliminate. It would seem that that's why it helps.
I am not a diabetic, but I've had idiopathic neuropathy for years. (We now know that it's from the B1 deficiency.) My neuropathy has improved ten-fold since I've started the shots. I do have some permanent nerve damage, but it's livable.
If I were in your shoes, I'd start my husband on Benfo right away. It can't hurt and has a good chance of helping. (I get mine from benfotiame.net) I've just started taking it myself.
The problem with the diet is people get sick from all the grease and fat and lack of carbs.
Yes, I want to know how you are doing it!
It’s great on your oatmeal, in your oatmeal cookies, on your baked apples and believe it or not in hamburger!!
isn’t your brain just full of fat?
have to leave and drink some olive oil....i am still looking for my weed pulling gloves...maybe it will come to me
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