Novel Alzheimer's Mechanism May Have Uncovered New Treatment Strategy

The specific cause of Alzheimer’s disease (AD) remains unclear and has even caused a Shakespearean-like feud among scientists with the amyloid family on one side not wanting to fraternize with the tau folks! Ok, perhaps that’s bit overdramatic, but researchers often ascribe to one AD theory over the other. However now, investigators at Rutgers University have discovered a new mechanism not involving either amyloid-beta or tau, which may contribute to AD, as well as traumatic brain injury, and is associated with a potassium ion-channel referred to as KCNB1.

Findings from the new study were published recently in Cell Death & Disease through an article titled “Oxidation of KCNB1 channels in the human brain and in mouse model of Alzheimer’s disease.”

The Rutgers team found that under conditions of stress, in a brain affected by Alzheimer’s, KCNB1 builds up and becomes toxic to neurons and then promotes the production of amyloid-beta. The build-up of KCNB1 channels is caused by a chemical process commonly known as oxidation.

“Indeed, scientists have known for a long time that during aging or in neurodegenerative disease cells produce free radicals,” explains senior study investigator Federico Sesti, Ph.D., professor of neuroscience and cell biology at Rutgers Robert Wood Johnson Medical School. “Free radicals are toxic molecules that can cause a reaction that results in lost electrons in important cellular components, including the channels.”

Interestingly, the researchers found that in brains affected by Alzheimer’s, the build-up of KCNB1 was much higher compared to normal brains.

“We reported that oxidation of KCNB1 channels is exacerbated in the postmortem brains of AD donors compared to age-matched controls,” the authors wrote. “In addition, phosphorylation of Focal Adhesion kinases and Src tyrosine kinases, two key signaling steps that follow KCNB1 oxidation, is also strengthened in AD vs. control brains.”

“The discovery of KCNB1’s oxidation/build-up was found through observation of both mouse and human brains, which is significant as most scientific studies do not usually go beyond observing animals,” Dr. Sesti adds. “Further, KCNB1 channels may not only contribute to Alzheimer’s but also to other conditions of stress as it was found in a recent study that they are formed following brain trauma.”

In the cases of Alzheimer’s and traumatic brain injury, the build-up of KCNB1 is associated with severe damage to mental function. As a result of this discovery, Dr. Sesti and his colleagues successfully tested a drug called Sprycel in mice. The drug is used to treat patients with leukemia.

“Our study shows that this drug and similar ones could potentially be used to treat Alzheimer’s, a discovery that leads the way to launch a clinical trial to test this drug in humans.”