To stop Alzheimer’s disease, a leading theory proposes reducing in-brain buildup of a protein fragment known as beta-amyloid. Scientists struggling to achieve this goal are, for example, testing a vaccine that prompts the immune system to clear this amyloid from the brain.
The solution may be even simpler. A study in mice suggests that ibuprofen, the common nonprescription drug, may lessen abnormal accumulation of beta-amyloid.
While this finding supports previous data indicating that ibuprofen and other nonsteroidal anti-inflammatory drugs (NSAIDs) slow or prevent the onset of Alzheimer’s disease, researchers say it also opens up a new way to think about how ibuprofen protects the brain.
“We’ve shown that a drug that’s available, that’s been in use for 30 to 40 years, and [for which] we know the side-effect profiles…can reduce both the inflammatory response to amyloid and the amyloid” itself, says study leader Gregory M. Cole of the University of California in Los Angeles.
About 20 studies have revealed that people who took NSAIDs for various reasons had a smaller risk—60 percent less in one study—of developing Alzheimer’s disease than people who didn’t take the drugs. Yet NSAIDs can cause serious stomach problems, including bleeding. Investigators therefore hesitate to recommend widespread use of the drugs until they can develop safer versions and confirm that the drugs do check the progression of Alzheimer’s disease.
At the same time, neuroscientists continue to look for the mechanisms by which NSAIDs defend the brain. There’s plenty of evidence that inflammation within the brain, prompted by amyloid deposits, activates immune cells and elicits harmful substances that destroy nerve cells. That led to the conjecture that NSAIDs interrupt this dangerous sequence.
Cole and his colleagues confirmed this idea in their mouse studies. They tested mice deliberately modified to carry a mutated gene that causes early-onset Alzheimer’s disease in people. These mice develop amyloid deposits, or plaques, as well as features of brain inflammation that show up in people with the disease.
Mice receiving ibuprofen in their daily meals, however, experienced much less inflammation, says Cole. For example, the investigators observed fewer active microglia, which are the brain’s immune cells, near amyloid plaques.
Compared to untreated mice, those receiving ibuprofen also had about half the number of plaques and half of the total amount of brain amyloid, the investigators report in the Aug. 1 Journal of Neuroscience. That finding surprised Cole because studies of brain tissue from deceased elderly people who had remained mentally coherent have not shown less amyloid among NSAID users than among the others. A similar study, reported 2 months ago, that examined the brains of people with Alzheimer’s disease offered the same conclusion.
“I’m not doubting [the mouse] data, but it’s not entirely logical as to why they got that result,” says Ian R.A. MacKenzie of the University of British Columbia in Vancouver, who conducted one of the studies of human brains. The research on people, he concedes, has its own limitations that leave open the question of whether ibuprofen lessens the amyloid burden in the brain.
Cole offers two theories of how the drug could act. It might alter the production of inflammatory chemicals that control microglia, prompting them to do a better job of clearing amyloid. Or it might decrease concentrations of inflammatory agents that trigger amyloid creation.
Whatever the mechanism, Cole suspects that ibuprofen may do better at preventing Alzheimer’s disease than at treating people already afflicted. He’s now arranging trials to evaluate the drug’s protective powers.