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
So, do you just reverse insulin resistance, and you won’t get Alzheimer’s?
The researchers had a cure, but after a bowl of ice cream, forgot it.
If that’s true, I wonder whether putting oldsters on a high protein diet would be useful.
If that’s true, I wonder whether putting oldsters on a high protein diet would be useful.
Seems to be a key element. If insulin resistance is a factor, it is possible to reverse the situation................
I wonder if cinnamon, which helps the body use insulin in people prone to Type II diabetes, would be of benefit to people who have Alzheimer’s in the family?
I may start putting cinnamon in my coffee!.............
10 years sooner, and we might have had the Gipper around for a bit longer...
“...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.”
Does the research for Alzheimer’s know why these ADDL’s form in the first place?
Mmmmm, I think it's delicious! But I - no pun initially intended - sometimes forget to dash some in, unless I'm at a Starbuck's or coffee shop.
OK, we have known about the Amyloid protein buildup associated with Alzheimer’s and other diseases for a decade or more. This paper shows the ADDLs interfere with migration of insulin receptors to dendritic regions where they must normally function. The root problem is the amyloid protein interference with the functional insulin receptors. It seems that treatment objective is still to reduce the amyloid deposits, which seems very unlikely, or more appropriately to prevent the ADDL deposition in the first place. I still don’t see a break-through in treatment or prevention of this dreaded disease. This paper is more about functional interference with insulin receptors associated with memory. This is just one more functional alteration associated with excessive amyloid deposition.
I’m sure this is just one piece of the overall puzzle. But it may point another researcher in the right direction.................
Agreed. So it’s hard to know whether or not standard diabetic treatments would be of any help. But I’m thinking that any treatment that decreases insulin resistance may be of help when we’re still in the pre-Alzheimer’s pre-diabetic phase...
There is no pre-treatment, but there is prevention. If it comes in a box or a bag, don’t eat it. Too many people today eat like cattle in a feedlot, and what do they eat? grain, and lots of it, including refined carbs and way too much sugar. Reduce grain consumption to 20% of today’s average human diet and most of these diseases will go away.
Thanks to MainFrame65 for the alert.
remember all those jelly beans on his desk?
Personal observation and a a few hundred articles in the nutrition literature, too numerous to post. Refined carbohydrate consumption is directly linked to insulin response and its effect on metabolism is profound.
Thanks! I tried to get to it earlier but the link wouldn’t work.............
A High Fat, Low Carbohydrate Diet Improves Alzheimer's Disease In Mice
Science Daily Mice with the mouse model of Alzheimer's disease show improvements in their condition when treated with a high-fat, low-carbohydrate diet. A report published today in the peer-reviewed, open access journal Nutrition and Metabolism, showed that a brain protein, amyloid-beta,which is an indicator of Alzheimer's disease, is reduced in mice on the so-called ketogenic diet.
I’m definitely ok with the “high fat” part!...............
So am I! but the catch is you have to eliminate nearly ALL carbs. Not so easy to do. I’m on a low carb diet now. No bread, no rice, no potatoes, no sugar, no pasta, no fun.
No beer, no wine, no alcohol.....................
Please add me to your ping list! Thanks!...........
Hold on there kemosabe. Alcohol isn't a carb :^)
I could be wrong, but I thought that high-protein diets were hard on the kidneys of the aged.
Me, too. But ... I have learned to make almost everything I love to eat (bread, waffles, cereal, cheesecakes, etc.) with very few carbs. And delicious, I might add.
I have lost 87 pounds, my blood sugar hovers between 85 & 92, and my blood pressure has dropped from 155/95 to 115/65. I still have ANOTHER 85-90 pounds to lose, but I would never go back to eating anything processed, or those high carb meals. I take no medications, either, other than vitamins.
Let me know if you need suggestions on making the low carb lifestyle delicious & fun. No need to feel deprived. (hint: Budweiser Select beer ... )
... jumping off soapbox now
“Atkins Alcohol Carb Chart
If you enjoy a cocktail before dinner, or a glass of wine with your steak, you’ll be happy to know that most alcohols are zero carb! This list is for straight alcohols, like beer, wine, gin, etc.
The carb counts given here are effective carb counts, with the fiber removed. All amounts here are for a 1oz shot, except as indicated.
Armagnac - 0g
Beer (12oz) - 12.5g
Bourbon - 0g
Brandy - 0g
Cognac - 0g
Gin - 0g
Rum - 0g
Scotch - 0g
Tequila - 0g
Vermouth, Dry - 1.4g
Vermouth, Sweet - 4.5g
Vodka - 0g
Whiskey - 0g
Wine, Red (4oz) - 2.0g
Wine, White (4oz) - 0.9g
Welcome aboard. Keep control out there.
Ping for later.
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.
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