An experimental treatment completely reversed Alzheimer’s disease in mice by reducing the levels of a single enzyme in the animals’ brains. The results further bolster the theory that amyloid plaques are at the root of this mysterious brain disease, and that addressing these plaques could lead to an eventual cure for Alzheimer’s.
The study, published February 14 in the Journal of Experimental Medicine, found that slowly reducing levels of the enzyme BACE1 in mice as they aged either prevented or reversed the formation of amyloid plaques in the brain, a hallmark sign of Alzheimer’s disease.
Amyloid plaques, formed when bits of protein clump together in the brain, are found in high amounts in Alzheimer’s patients. BACE1 is a protein that naturally forms in the brain and helps produce beta-amyloid peptide, a protein also involved with brain plaque formation.
Scientists at the Cleveland Clinic theorized that reducing BACE1 in the brain would have a trickle-down effect, reducing plaque formation. In their experiment, they examined mice bred to both develop Alzheimer’s and gradually produce less BACE1 enzyme as they age, the latter through the removal of a crucial gene. These mice should have developed Alzheimer’s disease, but without BACE1, they did not. Instead, they developed normally and remained healthy well into old age.
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The researchers observed that reducing BACE1 levels not only prevented Alzheimer’s in mice, but also reversed the disease in animals who had already begun to show signs.
Offspring of the original BACE1 knockout mice also showed a similar reduction in their BACE1 levels. But these offspring did not have the initial protection from the disease and eventually began to form brain plaques. As the second generation of mice continued to age, though, they continued to lose BACE1 activity. Eventually, their brain plaques began to disappear. By the end of the study, the mice offspring showed absolutely no plaques at all in their brain.
Dr. Richard Isaacson, director of the Alzheimer’s Prevention Clinic at NewYork-Presbyterian/Weill Cornell Medicine told Newsweek that the results were promising and added further evidence that BACE1 inhibitor could be an effective Alzheimer’s treatment. But he warned that it’s too early to celebrate just yet. Mice are too different from humans for us to take these results as anything.
“The completely other side of the coin is that 99 percent of all clinical drug trials [for Alzheimer’s disease] have failed, and we don’t know why,” said Isaacson, who was not involved in the new study. “Maybe amyloid [plaque buildups] isn’t the right target.”
And even if amyloids are the right target, Isaacson explained, we’d still have a minimum of five to seven years before we would know if the same approach is helpful in humans.
Still, Dr. Daniel Franc, a neurologist at Providence Saint John’s Health Center in Santa Monica, California, said that regardless of whether this exact finding can be successfully translated to humans, the results are still important.
“I would say that this is an incremental finding. It’s not revolutionary, but it does add further support to current ongoing approaches,” said Franc, adding that if anything, the research simply gives him hope that we are on the right path to finding a viable treatment. “I don’t think there has ever been a better time to think that we will have interventions for Alzheimer’s.”