Alzheimer’s disease is a slow, tragic blight of the brain – a disorder that intrudes upon a patient’s identity and fundamentally changes who they are. The condition is chronic and, at this point, incurable.
Now, researchers report that mice rid of a specific enzyme show signs of Alzheimer’s reversal – their amyloid plaques melted away, cognition improved, and their synaptic function was partially restored.
"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," says senior researcher Riqiang Yan, from the Cleveland Clinic Lerner Research Institute, in a statement.
The enzyme in question is called beta-secretase (BACE1). Its role, however, is not as straightforward as it may seem. The critical chunk of this research, published in The Journal of Experimental Medicine, is not exactly in BACE1’s importance, but in the timing of its use.
An early red flag of Alzheimer’s disease is the abnormal buildup of beta-amyloid peptide, which can form the notorious clumps of amyloid plaques in the brains of patients and disrupt their synaptic function.
Since BACE1 helps produce this unwanted beta-amyloid peptide, many companies are looking into how to knock back the enzyme. This is tricky, though, as BACE1 has many uses apart from its rather sinister role in unwanted plaque buildup.
Previous studies have found that mice who lack BACE1 suffer from neurodevelopment issues early on. This suggests that early in development, BACE1 is needed for healthy cognitive function.
If this is the case, the team decided to see if gradually depleting the enzyme in adulthood was less harmful than doing it early in development. To test this, the team genetically engineered mice to lose the enzyme as they aged. The mice were then bred with a different group of mice that were engineered to develop amyloid plaques when they were 75 days old.
The team found that the mice engineered to gradually lose BACE1 saw their amyloid plaque melt away. At the 10-month benchmark, the mice had no residual amyloid plaque left in their brains.
However, the study makes no claim of such success in humans. In fact, scientists have cured Alzheimer’s disease before in mice without replicating the results in patients. Instead, the hope lies in pointing researchers to drugs that could mimic a similar process in humans.
Good news for Yan’s team, BACE1-inhibitor drugs are currently in development, with around five such drugs being tested in clinical trials. So far, the results are mixed.
Yan hopes his team's study sparks further trial developments. Perhaps, he suggests, trials are starting BACE1 too late in the disease process to make a difference in the lives of Alzheimer’s patients.
A touch of timing, then, may be the key.
