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Researchers Reverse Alzheimer’s in Mouse Models

Brain plaques connected to Alzheimer’s disease disintegrated in mice when a key enzyme was removed, a new study finds, raising hopes that drugs targeting the enzyme may cause the same positive reversal of the neurological disease in humans.

The study, published in the Journal of Experimental Medicine on Wednesday, found that by removing the BACE-1 enzyme, the amyloid plaque in the brains of adult mice with Alzheimer’s disease not only stopped building up, but also dissolved away without negatively affecting their neuro-development.

“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,” senior researcher Riqiang Yan said in a press release.

Amyloid plaques that build up in the brain disrupt the ability of neurons to communicate. Limiting BACE1 activity also reversed the activation of microglial cells and the formation of abnormal neuronal processes that are connected to the brain disease, the study found.

The researchers expected that blocking BACE1 would slow or halt the formation of amyloid plaques, but they were surprised it also caused existing plaques to disintegrate, Yan told the Chicago Tribune.

 “When we looked at the mice later – at six months old and 10 months old – all those pre-existing plaques were gone,” Yan said. Further, the removal of the enzyme improved learning and memory of the mice with Alzheimer’s disease.

Five BACE1-inhibitor drugs are in the process of clinical trials as a potential treatment for Alzheimer’s disease, Yan said.

“Our data show that BACE1 inhibitors have the potential to treat Alzheimer’s disease patients without unwanted toxicity,” Yan said. Yan warned, though, that scientists and pharmaceutical companies need to minimize damage done from removing too much of the BACE1 enzyme, which is needed to cleave other proteins and can cause severe neurodevelopmental defects if completely removed.

 The study was conducted by a team of scientists from the Cleveland Clinic Lerner Research Institute.

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