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Is Alzheimer’s Diabetes?
Is Alzheimer's disease actually a kind of diabetes? New research is starting to support that idea. And as this ScienCentral news video reports, it could have implications for treating Alzheimer's.
Rethinking Alzheimer's
It takes a lot to convince Bill Klein of something so contrary to what he believed. For 30 years the Northwestern University neuroscientist, like many of his colleagues, did not believe that Alzheimer's disease had anything to do with diabetes.
"I told students who were saying that there might be a connection between diabetes and Alzheimer's disease that it just wasn't the case," recalls Klein.
But a collaboration with his colleague, Wei-Qin Zhao, showing that the brains of Alzheimer's patients are insulin resistant, began to change his mind.
Zhao "is one of the leaders in showing that insulin receptors in the brain are really important in learning and memory," says Klein.
In normal brains, brain cells process insulin, allowing memories to form. Klein explains that in people with Alzheimer's disease "what's happening is insulin is there but it's not effective — the receptors have become insensitive."
That's similar to type 2 diabetes, "where insulin is being made at least at the beginning but the body doesn't respond well to it and that's throughout the body," explains Klein.
So while type 2 diabetics suffer from insulin resistance in the body, Alzheimer's patients have insulin resistance in the brain.
"This is a brain-specific form of diabetes," he says.
ADDLed Brains
What finally convinced Klein was his own discoveries about toxic proteins called ADDLs ("addles"). Ten years ago, Klein and his colleagues discovered that ADDLs build up in the brains of Alzheimer's patients in addition to the plaques and tangles that are a well-known part of Alzheimer's pathology.
Klein's recent research, published in the FASEB Journal used rat brain cell cultures in the lab to study the effect of these ADDls on the insulin receptors. He and his team found that ADDLs attach near the insulin receptors, causing the receptors to disappear.
"So, even if there's insulin around now, the receptor isn't there to respond to it and we thing that's very crucial in blocking memory in Alzheimer's disease," says Klein.
"Type 3"
Klein says the evidence is strong enough to suggest that Alzheimer's may be a type 3 diabetes. He thinks modifying current diabetes drugs for delivery to the brain could bring new treatments for Alzheimer's disease. He would also like to find ways to fight the toxic ADDLs.
In the meantime, Klein says it's possible that regular exercise and staying lean — the recipe for keeping diabetes at bay — may also work for Alzheimer's.
He says discovering the mechanism of insulin resistance in rat brain cells does not refute previous research on the plaques and tangles found in Alzheimer's patient's brains. Rather it adds to the growing knowledge about this devastating disease.
Adds Klein, "Anything that we can find out about what cause the disease is good news for people with Alzheimer's disease. So what we have emerging here is new approaches and I think that's something to be excited about."
Study funded by: National Institutes of Health, The Alzheimer's Association, The American Health Assistance Foundation, and The Human Frontier Science Program.
Is Alzheimer's disease actually a kind of diabetes? New research is starting to support that idea. And as this ScienCentral news video reports, it could have implications for treating Alzheimer's.
Rethinking Alzheimer's
It takes a lot to convince Bill Klein of something so contrary to what he believed. For 30 years the Northwestern University neuroscientist, like many of his colleagues, did not believe that Alzheimer's disease had anything to do with diabetes.
"I told students who were saying that there might be a connection between diabetes and Alzheimer's disease that it just wasn't the case," recalls Klein.
But a collaboration with his colleague, Wei-Qin Zhao, showing that the brains of Alzheimer's patients are insulin resistant, began to change his mind.
Zhao "is one of the leaders in showing that insulin receptors in the brain are really important in learning and memory," says Klein.
In normal brains, brain cells process insulin, allowing memories to form. Klein explains that in people with Alzheimer's disease "what's happening is insulin is there but it's not effective — the receptors have become insensitive."
That's similar to type 2 diabetes, "where insulin is being made at least at the beginning but the body doesn't respond well to it and that's throughout the body," explains Klein.
So while type 2 diabetics suffer from insulin resistance in the body, Alzheimer's patients have insulin resistance in the brain.
"This is a brain-specific form of diabetes," he says.
ADDLed Brains
What finally convinced Klein was his own discoveries about toxic proteins called ADDLs ("addles"). Ten years ago, Klein and his colleagues discovered that ADDLs build up in the brains of Alzheimer's patients in addition to the plaques and tangles that are a well-known part of Alzheimer's pathology.
Klein's recent research, published in the FASEB Journal used rat brain cell cultures in the lab to study the effect of these ADDls on the insulin receptors. He and his team found that ADDLs attach near the insulin receptors, causing the receptors to disappear.
"So, even if there's insulin around now, the receptor isn't there to respond to it and we thing that's very crucial in blocking memory in Alzheimer's disease," says Klein.
"Type 3"
Klein says the evidence is strong enough to suggest that Alzheimer's may be a type 3 diabetes. He thinks modifying current diabetes drugs for delivery to the brain could bring new treatments for Alzheimer's disease. He would also like to find ways to fight the toxic ADDLs.
In the meantime, Klein says it's possible that regular exercise and staying lean — the recipe for keeping diabetes at bay — may also work for Alzheimer's.
He says discovering the mechanism of insulin resistance in rat brain cells does not refute previous research on the plaques and tangles found in Alzheimer's patient's brains. Rather it adds to the growing knowledge about this devastating disease.
Adds Klein, "Anything that we can find out about what cause the disease is good news for people with Alzheimer's disease. So what we have emerging here is new approaches and I think that's something to be excited about."
Study funded by: National Institutes of Health, The Alzheimer's Association, The American Health Assistance Foundation, and The Human Frontier Science Program.