Scientists have long sought to develop a vaccine that may prevent the onset or progression of Alzheimer’s disease. But so far, vaccines have had limited benefit and proved potentially dangerous, sometimes triggering life-threatening inflammation in the brain. Now, researchers say that giving a vaccine at an early stage, before symptoms and brain damage have become prominent, may be critical for getting a vaccine to work.
The researchers, from Georgetown University Medical Center in Washington, worked with lab rats that had been bred to develop a disease that resembles Alzheimer’s in humans. They found that the rodents with a large brain buildup of toxic amyloid protein, similar to the beta-amyloid protein that builds up in the brains of people with Alzheimer’s, were more likely to develop brain inflammation after receiving the vaccine than those with little buildup of the toxic protein. The animals with the least amyloid in the brain were also most likely to benefit from the vaccine, showing a slowing of symptoms suggestive of Alzheimer’s disease.
The results mean that people in the earliest stages of Alzheimer’s, who have little buildup of toxic beta-amyloid in the brain, may be the best candidates for an Alzheimer’s vaccine, since they may be least likely to suffer from toxic side effects of vaccine-induced inflammation. The findings were presented at the 2011 annual meeting of the Society for Neuroscience.
The results also call attention to the need for improved techniques to diagnose Alzheimer’s early, before buildup of beta-amyloid has extensively damaged the brain.
Several Alzheimer’s vaccines are currently being tested. Most target beta-amyloid, and some have shown limited success in preventing the buildup of the toxic protein in the brain. But in early experiments, some have had to be withdrawn from testing because they caused inflammation and brain swelling, both potentially dangerous, in a few patients.
The study is important, said Dr. R. Scott Turner, director of the Georgetown University Memory Disorders Program, because it shows that excessive inflammation occurs in brains that have a high burden of amyloid. The results suggest that benefits from the vaccine will most likely be found in those with less amyloid buildup, or so-called amyloid burden. The study also provides clues as to how and why the inflammation occurs, Dr. Turner says.
The researchers note that the vaccines now being tested in patients with Alzheimer’s may work better in patients with mild cognitive impairment, or MCI, a form of memory loss that sometimes precedes Alzheimer’s. They are currently recruiting patients for a trial of a vaccine in people with MCI.
“We may find that in the future, we will have to tailor immunization therapies based on amyloid burden in individual patients,” Dr. Turner said. People with more advanced disease, for example, may be given a vaccine tailored to minimize the risk of excessive inflammation in the brain.