Is Alzheimer's Disease Diabetes of the Brain?

Findings from a recent study suggest that Alzheimer’s Disease may be a diabetic disorder central to the brain. They have also found a way that could potentially be used to treat the disease.

In a study published by Molecular Psychiatry, investigators discovered a similarity in the way insulin signaling works in the brain of patients with Alzheimer’s disease, and the way it works in the pancreas of patients with diabetes.

Memantine is an N-methyl-D-aspartate receptor antagonist commonly used to treat Alzheimer’s disease and related dementias. The drug is known to block excess activity of glutamate, which reduces the symptoms of the disease.

Investigators discovered that memantine is also able to block the ATP-sensitive potassium channel (Kir6.2 channel). Inhibiting the Kir6.2 channel improves insulin signaling in the brain, according to the study.

“In the pancreas, the Kir6.2 channel blockade increases the insulin signaling, and insulin signaling decreases the blood glucose levels,” said researcher Shigeki Moriguchi, PhD. “In the brain, insulin signaling increases the acquisition of memory through CaM kinase II activation by Kir6.2 channel blockade.”

In mice models of Alzheimer’s disease, treatment with memantine was associated with improved impaired hippocampal long-term potentiation. They also discovered that these mice also had improved memory-related behaviors due to the inhibition of Kir6.2.

The investigators hypothesize that the blockage of Kir6.2 in the dendritic spines is able to regulate CaMKII activity through increasing intracellular Ca2+ mobilization, according to the study. Increased Ca2+ mobilization then improves cognitive function through assisting AMPAR trafficking into the postsynaptic membrane.

Currently, there is no cure for Alzheimer’s disease. Patients have very limited options that may help improve certain symptoms experienced.

These new findings suggest that Alzheimer’s disease is very similar to diabetes, and drawing parallels between the 2 diseases may help improve treatment options since patients with diabetes have multiple treatment options.

Investigators hope that these findings will prompt additional studies for novel drugs that inhibit the Kir6.2 channel for patients with Alzheimer’s disease.

“Since KATP channels Kir6.1 or Kir6.2 are critical components of sulfonylurea receptors (SURs) which is downstream insulin receptor signaling, the KATP channel inhibition by Memantine mediates the anti-diabetic drug action in peripheral tissues,” Dr Moriguchi concluded. “And this leads to improved cognitive functions and improved memory retention among Alzheimer's patients.”