Alzheimer's Thought To Be a Third Form of Diabetes

A new discovery has raised the possibility that the memory loss in individuals suffering from Alzheimer's disease could indicate that it might be a novel third form of diabetes.

Researchers at Northwestern University (Chicago, IL, USA) studied synapses implicated in learning and memory mechanisms, using mature cultures of hippocampal neurons, both before and after a toxic protein called amyloid ß-derived diffusible ligands (ADDLs)--found in the brains of individuals with Alzheimer's disease--were introduced. The researchers discovered that 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. By measuring the neuronal response to insulin, the researchers showed that ADDL removes insulin receptors from nerve cells, rendering those neurons insulin resistant. Together with other research showing that levels of brain insulin and its related receptors are lower in individuals with Alzheimer's disease, the new study supports the emerging idea of Alzheimer's being a type 3 diabetes. The study was published in the August 2007 issue of the journal of the Federation of American Societies for Experimental Biology (FASEB).

"We found the binding of ADDLs to synapses somehow prevents insulin receptors from accumulating at the synapses where they are needed,” said lead author William L. Klein, a professor of neurobiology and physiology. "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 Alzheimer's disease.”

"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 Dr. Fernanda G. De Felice, a visiting scientist from Federal University of Rio de Janeiro (Brazil). "These factors suggest that insulin resistance in the brains of those with Alzheimer's is a response to ADDLs.”

The researchers suggest that the study findings could help determine which aspects of existing drugs now used to treat diabetic patients may protect neurons from ADDLs and improve insulin signaling in individuals with Alzheimer's disease.


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Federal University of Rio de Janeiro
Northwestern University