Alzheimer’s May Share Similar Disease Mechanisms with Diabetes, Researchers Say

Magdalena Kegel avatar

by Magdalena Kegel |

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Alzheimer's and diabetes

After observing similarities in insulin molecular signaling between the pancreas and the brain, Japanese researchers suggest that Alzheimer’s disease is a form of diabetes condition that affects the brain.

Their study, “Blockade of the KATP channel Kir6.2 by memantine represents a novel mechanism relevant to Alzheimer’s disease therapy,” recently appeared in the journal Molecular Psychiatry.

The research team at the Graduate School of Pharmaceutical Sciences at Tohoku University in Japan noted that a drug used to treat Alzheimer’s disease called Namenda (memantine) blocks a potassium channel in the brain.

This channel, called Kir6.2, is involved in insulin signaling in the pancreas, and is important for diabetes processes. When the channel gets blocked in the pancreas, it increases insulin, which in turn reduces the levels of blood sugar.

The team performed experiments in mice, showing that blocking the channel with memantine improved long-term potentiaion in the hippocampus — a brain region crucial for memory formation. Long-term potentiation is a measure of the strength of connections between neurons, which is believed to underlie the memory-forming capacity of the brain.

When the team used another compound, which prevented the drug from blocking the potassium channels, the effects were lost.

The suspicion that the channel was involved in the memory-forming capacity of the mice was also confirmed by breeding mice that lacked the channel from birth. These animals showed severe memory problems and reduced long-term potentiation of nerve connection in the hippocampus.

“In the pancreas, the Kir6.2 channel blockade increases the insulin signaling, and insulin signaling decreases the blood glucose levels,” Dr. Shigeki Moriguchi, lead author of the study, said in a press release. “In the brain, insulin signaling increases the acquisition of memory … by Kir6.2 channel blockade.”

Namenda has long been used to improve cognition based on its ability to block another type of receptor — the glutamate NMDA (N-methyl-D-aspartate) receptor. When glutamate signaling through this receptor gets too intense, toxic processes start taking place.

And while large studies show that Namenda does improve cognition in Alzheimer’s, the effects are small.

The team now hopes their findings may pave the way for new treatments for Alzheimer’s disease, targeting the potassium channel in a way that produces more potent effects than Namenda.