Is Alzheimer’s a Form of Diabetes?

Insulin resistance specifically in the brain is being proposed as the reason for the memory loss that characterizes Alzheimer’s disease. Because Alzheimer’s may be caused by insulin-related dysfunction, some scientists are calling Alzheimer’s by a new name: type 3 diabetes.

Insulin, according to previous research, is produced in the brain as well as in the pancreas. During early Alzheimer’s, the brain’s insulin levels and the quantity of its insulin receptors fall quickly, and they continue to drop progressively as the disease advances. In its most advanced stage, an Alzheimer brain has nearly eighty percent fewer insulin receptors than a normal brain. Thus, insulin resistance in the brain is associated with Alzheimer’s disease.

Until now, exactly why the insulin receptors disappear has not been known. But now researchers from Northwestern University think they have it figured out.

First, here’s a short lesson on how neurons (brain cells) communicate. Neurons have three parts: tree-shaped dendrites, a cell body, and a long axon. To get from one neuron to the next, information from the first neuron flows from its cell body, down its axon, then across a little space called a synapse, to the dendrites of the next neuron. When all is working well, insulin binds to insulin receptors on the dendrites at a neuron’s synapse, turning on a mechanism necessary for nerve cells to survive and memories to form.

But now researchers have found that a toxic protein in the brains of Alzheimer’s patients prevents insulin receptors from setting up for business at the neuronal dendrites. The toxic proteins, called ADDLs (short for “amyloid beta-derived diffusible ligands”), are small proteins that accumulate at the beginning of Alzheimer’s disease. ADDLs bind to the neuron dendrites, hogging the spots and preventing insulin receptors from gathering there.

As a result, the insulin receptors pile up in the cell bodies where the insulin can’t get to them. Because the bound ADDLs prevent the insulin receptors from getting near the synapses, there is a rapid loss of insulin receptors from the dendritic surfaces of the neurons. This is why nerve cells become insulin resistant in Alzheimer’s.

The researchers found that neurons that had ADDLs bound to them had no insulin receptors on their dendrites. Conversely, the dendrites with lots of insulin receptors had no bound ADDLs. They think that ADDLs, because they block the insulin receptors from reaching the synapses, are a major factor in the memory deficits in Alzheimer’s patients. In fact, they believe that insulin resistance in the Alzheimer brain is a response to ADDLs, which, by disrupting insulin signaling, are causing a brain-specific form of diabetes.

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Sources: The FASEB Journal; BBC News; Diabetes in Control; Science Daily, September 2007

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