A Vaccine for Alzheimer’s? Antibody Clears Brain Plaques in Mice

In a mice study, researchers have developed an antibody to clears amyloid plaques, a hallmark of Alzheimer’s.

Most scientists believe that Alzheimer’s is caused by a build-up of beta-amyloid, a sticky protein, in the brain. Whether this is because the brain produces too much or because it loses the ability to clear the plaque, scientists are still trying to suss out. One thing is for sure: When the brain has too much beta-amyloid, it forms into plaques that cause neuron death, which leads to the breakdown of memory and communication between parts of the brain.

Scientists at Washington University School of Medicine may have found a weapon to fight against this build-up. They developed an antibody that was able to clear the plaques in mice that were genetically engineered to develop Alzheimer’s. Study authors hope the findings will light the way to a treatment that could clear the plaques before the symptoms have a chance to develop.

“Many people build up amyloid over many years, and the brain just can’t get rid of it,” said senior author David Holtzman, MD, head of the Department of Neurology. “By removing plaques, if we start early enough, we may be able to stop the changes to the brain that result in forgetfulness, confusion and cognitive decline.”

“Many people build up amyloid over many years,
and the brain just can’t get rid of it.”

Scientists now know that beta-amyloid starts to build up decades before Alzheimer’s symptoms start to show, up to 30 years before a diagnosis is likely. There’s still no effective treatment for Alzheimer’s, but most researchers now agree that in order to stop it in its tracks, it needs to be treated much earlier, before patients are symptomatic.

One way to get rid of the plaques is to target them with antibodies, but past studies have shown that doing so can trigger inflammation, which is also tied to Alzheimer’s. Instead, the Washington University researchers targeted a protein called ApoE, which is bundled inside of the plaques. Most humans have one of three variants of ApoE, and certain variants are considered the single most telling factor in whether a person will develop Alzheimer’s. When the antibody binds with ApoE, it attracts immune cells, which destroy it.

“By removing plaques, if we start early enough,
we may be able to stop the changes to the brain that
result in forgetfulness, confusion and cognitive decline.”

In the experiment on mice, when the ApoE was destroyed, the plaques were destroyed along with it. Mice who were injected with the antibody, called HAE-4, had 50 percent fewer plaques than they did before they were injected.

“It turns out that the ApoE in the plaques has a
different structure than the form of APOE found in the blood.
The HAE-4 antibody recognized only the form
found attached to the plaques in the brain.”

What’s more, this antibody targeted only ApoE in the brain, even though it also exists in the blood. Because ApoE transports fats in the bloodstream, removing it could be dangerous.

“It turns out that the ApoE in the plaques has a different structure than the form of APOE found in the blood,” Holtzman said. “The HAE-4 antibody recognized only the form found attached to the plaques in the brain.”

Next, the researchers plan to prepare the antibody for trials in humans.

This study was published in The Journal of Clinical Investigation.