Alzheimers and Diabetes

Scientists Think Alzheimer's is Form of Diabetes

Could Alzheimer’s disease in fact be another form of diabetes? This novel research conclusion indicates that the memory loss associated with Alzheimer’s could be what some are calling a “third type” of diabetes, possibly treatable with insulin.

A scientific research team at Northwestern University says it has discovered why brain insulin signaling, which is a critical task during memory formation, stops working when one develops Alzheimer’s disease. They found that a toxic protein called an ADDL, which is resident in Alzheimer’s patients, removes insulin receptors from nerve cells, resulting in those neurons becoming resistant to insulin. ADDL is an acronym for "amyloid ß-derived diffusible ligand."

With other research showing that levels of brain insulin and its related receptors are lower in individuals with Alzheimer's disease, the Northwestern study supports the emerging idea of Alzheimer's being a "type 3" diabetes.

"We found the binding of ADDLs to synapses somehow prevents insulin receptors from accumulating at the synapses where they are needed," the Northwestern research team leader, William L. Klein, said in a statement.

"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 of why nerve cells should become insulin resistant in Alzheimer's disease."


The new findings, published online in the Federation of American Societies for Experimental Biology 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 Alzheimer's.

Insulin and insulin receptors in the brain are vital to learning and memory. When insulin binds to a receptor at a synapse, it switches on a mechanism necessary for nerve cells to survive and memories to form. That Alzheimer's may in part be caused by insulin resistance in the brain has scientists asking how that process gets initiated.

ADDLS are small, soluble aggregated proteins. Clinical data strongly supports a theory in which ADDLs accumulate at the beginning of Alzheimer's 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 Alzheimer's brains," said Klein, a member of Northwestern's Cognitive Neurology and Alzheimer's Disease Center. "We're dealing with a fundamental new connection between two fields, diabetes and Alzheimer's 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."

Klein said he believes derivatives of drugs currently used to treat type 2 diabetes may hold treatment promise for Alzheimer’s. "With proper research and development the drug arsenal for type 2 diabetes, in which individuals become insulin resistant, may be translated to Alzheimer's treatment," said Klein. "I think such drugs could supersede currently available Alzheimer's drugs."

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