In the study published in the Journal of Experimental Medicine on Feb. 14, researchers found that gradually depleting the enzyme called BACE1 can reverse the formation of amyloid plaques in the brain, which can then improve cognitive functions of the lab animals. The finding offers hope that a BACE1-targeting drug can eventually cure Alzheimer's Disease in humans.
The earliest sign of Alzheimer's disease is the abnormal buildup of beta-amyloid peptide, which leads to the formation of amyloid plaques in the brain that affects the neuronal synapses and causes memory loss.
Studies have shown that stopping or reducing the activity of the BACE1 can reduce the production of the beta-amyloid peptides. Unfortunately, the enzyme also controls many important processes in the body, which means that BACE1-inhibiting drugs may have serious side effects. Researchers, for instance, have found that mice lacking BACE1 have severe neurodevelopmental defects.
In the new study, Cleveland Clinic researcher Riqiang Yan and colleagues investigated the effects of gradually depleting they enzyme in mice as they grow older. They found that the animals developed normally. The researchers then bred these animals with those that start to develop Alzheimer's disease.
The researchers found that the offspring formed plaques at 75 days old, even though the levels of BACE1 were about 50 percent lower than normal. Nonetheless, these plaques disappeared as the rodents continued to age. At 10 months old, the mice had no plaques in their brain at all.
Reducing the activity of the BACE1 also led to lower beta-amyloid peptide levels and reversed other hallmarks of Alzheimer's disease. It led to improved memory and learning as well.
"When we looked at the mice later - at six months old and 10 months old - all those pre-existing plaques were gone," Yan said. "Sequential deletion of beta-secretase actually can reverse existing plaques."
Hope For Alzheimer's Disease Patients
Researchers said that the findings offer hope that BACE1 inhibitors could be safely used to treat those suffering from Alzheimer's disease, which is currently the sixth leading killer in the United States.
"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," the researchers wrote in their study.