In Alzheimer's, BACE1 Inhibition May Reverse Amyloid Deposition


In Alzheimer's, BACE1 Inhibition May Reverse Amyloid Deposition

In Alzheimer's, BACE1 Inhibition May Reverse Amyloid Deposition

In Alzheimer's, BACE1 Inhibition May Reverse Amyloid Deposition

Yan said that, as far as they are aware, "this is the first observation of amyloid deposits in any study of Alzheimer's disease in mice".

It improved the rodents' cognitive function - boosting learning and memory, a team at Cleveland Clinic Lerner Research Institute, US, found.

Drugs targeting this enzyme will be able to successfully treat Alzheimer's in humans, the researchers said. In many trials, mice completely lacking BACE1 suffer severe neurodevelopmental defects.

Dr Riqiang Yan, of the Cleveland Clinic Lerner Research Institute in the USA, said: "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". The results were remarkably positive, with the reduction in BACE1 activity not only stalling the development of amyloid plaques in the mice, but actually removing the deposits that had already formed. However, the plaques began to disappear as the mice continued to age and lose BACE1 activity, until, at 10 months old, the mice had no plaques in their brains at all.

This study provides "genetic evidence" that amyloid deposits "can be completely reversed after the gradual and increased elimination of BACE1 in adults".

Lead author Riqiang Yan envisions a future when these enzymes, known as BACE1 inhibitors, could be available as a vitamin that all humans take preventatively to stave off neurodegenerative disease.

However, electrophysiological recordings of neurons from these animals showed that depletion of BACE1 only partially restored synaptic function, suggesting that BACE1 may be required for optimal synaptic activity and cognition, Yan said.

Despite some compelling recent scientific breakthroughs in Alzheimer's research over the past year, several high-profile clinical trial failures have resulted in some big companies pulling back their investments in the area.

Other teams at the institute are also designing tests for the early detection of dementia risk and looking for ways to slow or prevent the spread of toxic proteins such as beta-amyloid and tau, which destroy certain nerve cells in the brain.

Past year a trial of a drug developed by pharceutical giant Merck was abandoned before it could be completed after disappointing results.

The findings could be a game changer for the pharmaceutical industry, which has had a rough ride with BACE1 inhibitors - although some analysts claim Merck's failure suggests we are barking up the wrong tree. That is now in phase 3 clinical trials.

Drugs that inhibit BACE1 are therefore being developed as potential Alzheimer's disease treatments but, because BACE1 controls many important processes by cleaving proteins other than APP, these drugs could have serious side effects.