Researchers develop method to reverse Alzheimer’s disease in mouse models

Researchers from the Cleveland Clinic’s Lerner Research Institute have discovered that selectively removing a particular enzyme from the brain can lead to a reversal of the formation of amyloid plaques, which are known to be linked with Alzheimer’s disease. After performing tests on lab mice, the researchers found that they could improve the cognitive function of the animals. In a detailed study, they concluded that the use of certain drugs to target this enzyme could help in treating Alzheimer’s disease in human patients.

The enzyme that was gradually removed by the researchers is none other than BACE1, which is also known as beta-secretase. It’s an enzyme that’s responsible for helping the body produce beta-amyloid peptide through cleaving amyloid precursor protein (APP). The researchers demonstrated in their study that by inhibiting BACE1, amyloid buildup could be hindered as a result. There are already drugs that inhibit BACE1 in development, but experts are worried that the use of such could lead to serious side effects, as the enzyme can also be used in other important processes.

According to Riqiang Yan, a senior researcher on the study, no one else has been able to demonstrate what they did in earlier studies. “To our knowledge, this is the first observation of such a dramatic reversal of amyloid deposition in any study of Alzheimer’s disease mouse models,” he said. The researchers noted that the depletion if the BACE1 enzyme also led to a reversal of the activation of microglial cells and the formation of abnormal neuronal processes, all of which are connected to Alzheimer’s disease.

What’s even more interesting is that it looked like the method used by the researchers ended up completely reversing the damage caused by Alzheimer’s disease, insofar as removing all pre-existing amyloid plaque build up. “When we looked at the mice later – at six months old and 10 months old – all those pre-existing plaques were gone,” explained Yan. “Sequential deletion of beta-secretase actually can reverse existing plaques.”

At the moment, the handful of drugs being developed as potential inhibitors of BACE1 are undergoing clinical trials. The problem is that they haven’t been entirely effective, with all of them showing mixed results. However, Yan said that the drugs might have just been given a little too late to patients, by which point the treatment simply has no chance to become effective.

Yan maintains that the difference between the effectiveness of the BACE1 inhibitor drugs that are in development and their own research results is down to timing. “Our findings should assure the pharmaceutical companies that if you treat people early enough, it not only can stop the growth of those plaques,” he said, “but will likely help to even remove the existing plaque.”

When you consider the fact that there is a known link between amyloid buildup and the development of Alzheimer’s disease, then you’ll realize that Yan’s statement does indeed make sense. Another thing worth noting from their research is that the complete and sudden removal of BACE1 isn’t a method that works. Instead, the gradual depletion of the enzyme is what makes it so effective, as the process has been shown to be non-toxic and not cause any other major detrimental effects.

In the future, the researchers hope to develop strategies that can help minimize the issues that do arise due to the depletion and removal of BACE1. Until then, their method will serve as a mere proof-of-concept on which later studies can be built upon.

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