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Discovery supports theory of Alzheimer's disease as form of diabetes
http://www. physorg. com/ news110029762. html
September 26, 2007
Insulin, now proven to be as crucial for the "mind" as it is for the body. Recent years of research have suggested the possibility that the memory loss in Alzheimer's disease (Alzheimer's, senile dementia) could be a "third type" of diabetes. (Note: Currently, there are Type 1 and Type 2 diabetes.)
Scientists at Northwestern University have discovered why brain insulin signaling—so critical for memory formation—stops working in individuals with Alzheimer's. They have demonstrated that the toxic proteins found in the brains of Alzheimer's patients remove insulin receptors from nerve cells, rendering those neurons insulin resistant. (This protein, known to attack memory-forming synapses, is called ADDL, "amyloid β-derived diffusible ligand.")
In addition to other studies confirming that levels of brain insulin and its related receptors are lower in Alzheimer's patients, Northwestern University's research suggests the idea that Alzheimer's is a "Type 3" diabetes.
This new discovery, published online in the FASEB Journal, will help researchers determine which existing drugs used to treat diabetes patients can protect neurons from ADDLs and improve insulin signaling in Alzheimer's patients.
In the brain, insulin and insulin receptors are crucial for learning and memory. When insulin binds to receptors located at synapses, it activates a mechanism necessary for the survival of nerve cells and memory formation. Alzheimer's patients, to some extent, suffer from insulin resistance in the brain, leading scientists to question how this process begins.
"We found that ADDLs bind to synapses, somehow preventing insulin receptors from accumulating at the synapses where they are needed," said William L. Klein, a professor of neurobiology and physiology at the Weinberg College of Arts and Sciences, who led the research team. "Instead, they accumulate at the cell body where they are made, near the nucleus. Insulin cannot reach the receptors there. This discovery is the first molecular evidence explaining why nerve cells in Alzheimer's patients become insulin resistant."
ADDLs are small, soluble aggregated proteins. Clinical data strongly support the theory that ADDLs begin to accumulate in the early stages of Alzheimer's and block memory function in a process that is expected to be reversible.
In earlier studies, Klein and colleagues found that ADDLs bind specifically to synapses, causing them to degenerate and leading to changes in the composition and shape of the synapses.Now Klein and his team have confirmed that the insulin receptors, the molecules responsible for memory formation at synapses, are removed from the surface of nerve cell membranes by ADDLs.
"We believe this is the primary reason for memory deficits in the brains of Alzheimer's patients caused by ADDLs," said Klein, a member of the Cognitive Neurology and Alzheimer's Disease Center at Northwestern University. "We are addressing the fields of diabetes and Alzheimer's with a new fundamental connection, and it involves medical approaches. We want to find ways to make these insulin receptors themselves resist the impact of ADDLs. And that might not be as difficult as it seems."
Using mature hippocampal neuron cultures, Klein and his team studied the synapses involved in learning and memory mechanisms. Neurons with significant differences could be studied at the molecular level. Researchers examined the synapses and their insulin receptors before and after the introduction of ADDLs.
They found that the toxic proteins caused a rapid and significant reduction of insulin receptors from the surface of neurons, particularly in the dendrites where ADDLs bind. The binding of ADDLs clearly disrupted the trafficking of insulin receptors, preventing them from reaching the synapses. Researchers measured the neural response to insulin and found it was greatly inhibited by ADDLs.
"In addition to discovering that neurons bound with ADDLs actually lack insulin receptors in their dendrites, we also found that dendrites with a large number of insulin receptors did not have ADDLs bound to them," said co-author Fernanda G. De Felice, a visiting scientist from the Federal University of Rio de Janeiro, who is working in Klein's lab. "These factors suggest that insulin resistance in the brains of Alzheimer's patients is a response to ADDLs."
"Using drugs specifically developed for type 2 diabetes, which are for people with insulin resistance, might be transformed into treatments for Alzheimer's patients," Klein said. "I think such drugs might now become incredibly useful for Alzheimer's patients."
Source: http:/ / only- perception. blogs……m/ 2007/ 09/ blog- post_568. html
Study: Alzheimer's Disease is "Type 3" Diabetes!
http://www. physorg. com/ news110029762. html
September 26, 2007
Insulin, now proven to be as crucial for the "mind" as it is for the body. Recent years of research have suggested the possibility that the memory loss in Alzheimer's disease (Alzheimer's, senile dementia) could be a "third type" of diabetes. (Note: Currently, there are Type 1 and Type 2 diabetes.)
Scientists at Northwestern University have discovered why brain insulin signaling—so critical for memory formation—stops working in individuals with Alzheimer's. They have demonstrated that the toxic proteins found in the brains of Alzheimer's patients remove insulin receptors from nerve cells, rendering those neurons insulin resistant. (This protein, known to attack memory-forming synapses, is called ADDL, "amyloid β-derived diffusible ligand.")
In addition to other studies confirming that levels of brain insulin and its related receptors are lower in Alzheimer's patients, Northwestern University's research suggests the idea that Alzheimer's is a "Type 3" diabetes.
This new discovery, published online in the FASEB Journal, will help researchers determine which existing drugs used to treat diabetes patients can protect neurons from ADDLs and improve insulin signaling in Alzheimer's patients.
In the brain, insulin and insulin receptors are crucial for learning and memory. When insulin binds to receptors located at synapses, it activates a mechanism necessary for the survival of nerve cells and memory formation. Alzheimer's patients, to some extent, suffer from insulin resistance in the brain, leading scientists to question how this process begins.
"We found that ADDLs bind to synapses, somehow preventing insulin receptors from accumulating at the synapses where they are needed," said William L. Klein, a professor of neurobiology and physiology at the Weinberg College of Arts and Sciences, who led the research team. "Instead, they accumulate at the cell body where they are made, near the nucleus. Insulin cannot reach the receptors there. This discovery is the first molecular evidence explaining why nerve cells in Alzheimer's patients become insulin resistant."
ADDLs are small, soluble aggregated proteins. Clinical data strongly support the theory that ADDLs begin to accumulate in the early stages of Alzheimer's and block memory function in a process that is expected to be reversible.
In earlier studies, Klein and colleagues found that ADDLs bind specifically to synapses, causing them to degenerate and leading to changes in the composition and shape of the synapses.Now Klein and his team have confirmed that the insulin receptors, the molecules responsible for memory formation at synapses, are removed from the surface of nerve cell membranes by ADDLs.
"We believe this is the primary reason for memory deficits in the brains of Alzheimer's patients caused by ADDLs," said Klein, a member of the Cognitive Neurology and Alzheimer's Disease Center at Northwestern University. "We are addressing the fields of diabetes and Alzheimer's with a new fundamental connection, and it involves medical approaches. We want to find ways to make these insulin receptors themselves resist the impact of ADDLs. And that might not be as difficult as it seems."
Using mature hippocampal neuron cultures, Klein and his team studied the synapses involved in learning and memory mechanisms. Neurons with significant differences could be studied at the molecular level. Researchers examined the synapses and their insulin receptors before and after the introduction of ADDLs.
They found that the toxic proteins caused a rapid and significant reduction of insulin receptors from the surface of neurons, particularly in the dendrites where ADDLs bind. The binding of ADDLs clearly disrupted the trafficking of insulin receptors, preventing them from reaching the synapses. Researchers measured the neural response to insulin and found it was greatly inhibited by ADDLs.
"In addition to discovering that neurons bound with ADDLs actually lack insulin receptors in their dendrites, we also found that dendrites with a large number of insulin receptors did not have ADDLs bound to them," said co-author Fernanda G. De Felice, a visiting scientist from the Federal University of Rio de Janeiro, who is working in Klein's lab. "These factors suggest that insulin resistance in the brains of Alzheimer's patients is a response to ADDLs."
"Using drugs specifically developed for type 2 diabetes, which are for people with insulin resistance, might be transformed into treatments for Alzheimer's patients," Klein said. "I think such drugs might now become incredibly useful for Alzheimer's patients."
Source: http:/ / only- perception. blogs……m/ 2007/ 09/ blog- post_568. html