🔑The key would be in blocking an enzyme: BACE1. Will this technique work in humans❓

A study carried out by experts at the Cleveland Clinic Lerner Research Institute in Ohio (USA) revealed that attacking an enzyme called BACE1 can "completely reverse" the accumulation of beta-amyloid plaque in the brain, which is a hallmark of Alzheimer's disease. For now, the findings are limited to mice, but they offer the hope that humans will one day be able to benefit from the same treatment.

The researchers, by Riqiang Yan of the Department of Neuroscience at the University of Connecticut School of Medicine, explain that the enzyme in question helps produce the beta-amyloid peptide. An excessive accumulation of this peptide eventually leads to brain pathologies related to Alzheimer's known as beta-amyloid plaques.

The BACE1 enzyme manages to do this by "cleaving" or breaking down a protein called amyloid precursor protein and also other proteins that regulate important processes in the brain. Inhibiting it with drugs is tricky because because BACE1 controls many important processes by cleaving proteins other than APP (amyloid precursor protein), these drugs could have serious side effects.

In fact, previous research has shown that the cancellation of the BACE1 gene in mice leads to defects in the development of axons of neurons, causing insufficient myelination and even depression.

Therefore, in the new study, the researchers intended to reduce this enzyme more smoothly and gradually, with the hope that it would produce better results with fewer side effects. Thus, they genetically engineered mice that would lose this enzyme little by little, as they got older.

🔙 Reversed disease completely

The mice developed perfectly normal in adulthood. They proceeded to raise them with other rodents that had symptoms similar to Alzheimer's, such as the accumulation of amyloid plaque in the brain.

The subsequent offspring of the rodents also began to accumulate plaque in their brains from a fairly early age. But as they got older, and they lost more BACE1 enzyme, their plaques began to gradually disappear. In fact, at 10 months, the mice did not have detectable beta-amyloid plaques.

This was not the only sign that the enzyme loss helped reverse Alzheimer's: amyloid beta-peptide levels in mice also decreased, and microglia, brain cells that, when activated, had previously correlated with density of the amyloid plaque, now they were off.

In addition, these neuronal changes were also reflected in the memory and learning skills of the mice, which also improved.

"As far as we know, this is the first observation of such a dramatic reversal of amyloid deposition in any study of mouse models with Alzheimer's disease," explains Riqiang Yan, leader of the work. "Our data show that inhibitors of BACE1 have the potential to treat patients with Alzheimer's disease without unwanted toxicity," he says.

MuyInteresante/jem

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