It is has been known for decades now that in Alzheimer’s disease, the brain becomes riddled with sticky deposits of a protein called amyloid beta. These deposits are referred to as plaques. But scientists have been trying to answer a key question—are the plaques the result of the brain’s over-production of amyloid beta, or are they caused by a breakdown in the mechanisms that metabolize the protein and eliminate it from the brain? The results of a study led by Dr. Michael Irizarry at Massachusetts General Hospital may provide an intriguing clue to help scientists solve the mystery.
In a paper published in the Archives of Neurology, Dr. Irizarry’s team reported their findings from a study designed to illuminate the role of a simple enzyme that clips amyloid beta protein into smaller fragments and is thought to help clear it from the brain. Referred to as BACE, the enzyme has long been suspected as a possible troublemaker. Proteins that are not shaped correctly due to faulty cleaving or cutting—a process usually performed by enzymes—are useless to the body, and may aggregate in areas where they don’t belong.
Dr. Irizarry and his colleagues first developed techniques to screen brain tissue for the presence of the BACE enzyme and to measure its level. Then they compared the enzyme levels in the Alzheimer’s-affected brain tissue with those of non-diseased brains. In one region, which is especially affected by Alzheimer’s plaques, the temporal neocortex, the BACE activity in the Alzheimer’s brains were 63% higher than in the healthy brains.
Discovering an overabundance of BACE in the regions of plaque formation seems to suggest that the pathological process of Alzheimer’s disease begins before plaques form. Amyloid beta may not be the actual culprit—a failure to efficiently clear it from the brain may be. All this means that eliminating amyloid beta after it has accumulated may not be the best treatment strategy. There may be a way to address Alzheimer’s disease earlier on, before the disease has destroyed too many irreplaceable brain cells.
The BACE enzyme will now be the target of possible drugs designed to block its production or its actions in the brain. Blocking this enzyme could turn out to be the key to halting Alzheimer’s disease before it can run its brain-destroying course