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Some genetic engineering, and a bit of breeding, have allowed a team of researchers at the Cleveland Clinic to create mice that have shown the ability to reverse Alzheimer’s Disease.

How the specialized laboratory model showing the reversal of amyloid plaque buildup could be translated to therapies in humans is work for the future, add the authors, in the paper in The Journal of Experimental Medicine.

“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,” said Riqiang Yan, currently of the Clinic’s Lerner Research Institute.

The target enzyme is called BACE1, which is also known as beta secretase. It helps create the beta-amyloid peptides – the plaques – which mark Alzheimer’s by cleaving amyloid precursor protein (APP).

But BACE1 is also important in growth and development, and can’t just be completely done away with, without serious biological consequences: abnormal astrogenesis, reduced neurogenesis, hyperactivities, hypomyelination, long-term depression, and muscle defects, among other side effects.

So the Cleveland Clinic researchers genetically engineered mice that gradually lose the enzyme as they grow older, they report.

Those mice were then bred with another group, which started to develop plaque and Alzheimer’s in their brains at an early age, before 3 months of age.

The offspring also started to develop the plaques at the same early age, the scientists write. But the plaques then begin to disappear because of the decreasing BACE1, they add. By the age of 10 months, the plaques have virtually disappeared, according to their description of the experimental models.

“In this study, we provide genetic evidence that sequential and gradually increased deletion of BACE1 not only reverses existing amyloid plaques, but also reduces gliosis and neuritic dystrophy and improves synaptic functions,” they write.

The mice who showed the ability to overcome the plaques also showed appropriate fear conditioning, and appeared to score normally on other behavioral tests, they add.

“Our data show that BACE1 inhibitors have the potential to treat Alzheimer’s disease patients without unwanted toxicity,” said Yan, who is expected to lead the Cleveland Clinic to become chair of neuroscience at the University of Connecticut this year.

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