Scientists Remove Alzheimer’s Brain Plaques in Mice
MONDAY, March 26, 2018 (HealthDay News) — New animal research shines a light on a therapy designed to rid the brain of much of the sticky amyloid plaque associated with early stage Alzheimer's disease.
Experts have long viewed plaque buildup as a largely symptomless marker for future Alzheimer's risk, with many believing the process is a root cause of the disease.
But unlike prior anti-amyloid efforts, the new therapy narrowly targets a specific protein — called APOE — lodged within such plaque buildup.
In mice genetically engineered to host human APOE, anti-APOE injections successfully reduced overall plaque buildup by as much as half, the researchers reported.
"The plaque that builds up is felt to initiate the process we know of that ultimately leads to the cognitive decline we see in Alzheimer's disease," said study author David Holtzman. "There is a lot of evidence that amyloid plaques are the instigator, or the trigger, of Alzheimer's disease."
The general feeling is that if you remove them early enough in the disease process, you might be able to delay or slow the disease, explained Holtzman. He is chair of neurology at the Washington University School of Medicine in St. Louis.
According to the Alzheimer's Association, 5.7 million Americans — mostly seniors — have Alzheimer's. It's the sixth leading cause of death in the United States. There is no known cure, and no effective means for slowing the disease's progression.
For this study, investigators focused on mice genetically prone to developing amyloid plaque, swapping out their APOE genes for human genes.
Over six weeks, different mice were exposed to different once-weekly antibody injections, while others were given dummy injections.
To differing degrees, the APOE antibody injections activated each mouse's immune system, causing it to destroy the human APOE.
In turn, when the investigators measured brain plaque post-therapy, they found significantly reduced overall amyloid buildup. For example, plaque levels plunged by half following one particular antibody therapy (HAE-4).
Still, Holtzman acknowledged, "it is not clear that removing (amyloid plaque) would eliminate Alzheimer's disease."
And he cautioned that moving from animal trials to human trials is a big leap, with uncertain results.
"The treatment we developed would need to be turned into a molecule that is safe to give to humans, and then be tested in humans," Holtzman explained. And such preparation for a human trial has not yet begun, he said.
Keith Fargo, director of scientific programs and outreach for the Alzheimer's Association, seconded that point.
"This is a mouse study, and it's not always the case that animal studies translate into anything that would be beneficial to humans at a later date," Fargo said.
"But I will say that I think there's something potentially very exciting here," he added.
Fargo noted that prior antibody studies were aimed at eliminating amyloid plaque as a whole — rather than APOE specifically. And those approaches sparked problematic side effects in some patients.
"Alzheimer's disease right now is fatal, so most people would be willing to take a drug even with the small risk of side effects," he said. "But it would be ideal if we didn't have to worry about it at all. So if you could target APOE directly, you might be able to clear the amyloid out of the brain that way."
However, Fargo cautioned that much work remains to be done. "This is not going to become a medication — if it ever does — in the next few years," he said. "This is going to be many years down the road."
The findings were published March 26 in the Journal of Clinical Investigation.
More information
The Alzheimer's Association dispels some myths about the disease.
There's also information on how to get involved with Alzheimer's research.
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