In a normal response to a viral infection like the flu, the immune system recognizes the virus as foreign, produces inflammation to clear it away, and then returns to its balanced, baseline function. For killer pathogens like polio, measles, and smallpox, the immune system needs help from vaccines—a form of immunotherapy—to make antibodies that bind to and remove the viruses.
As early as the 1890s, scientists have studied whether a similar inoculation approach could cure cancer and other non-communicable diseases. Today, there is a surging movement to develop a vaccine for Alzheimer’s disease, which would teach the immune system to recognize the first signs of the disease’s signature amyloid plaques and tau protein tangles and break them down.
Working in the Ann Romney Center for Neurologic Diseases at Brigham and Women’s Hospital, neurology investigator Cynthia Lemere, PhD, is piecing together how inflammation in the brain contributes to Alzheimer’s disease, and whether Alzheimer’s might be prevented, delayed, or slowed by immunotherapies containing antibodies that bind to a disease-specific form of amyloid-β protein, which forms plaques years before the cognitive decline caused by the disease.
“I’ve looked at a lot of brains with Alzheimer’s disease, and when I do, I see a lot of angry immune cells,” Lemere says.
We’ve always thought of the brain as being separate from the rest of the body that is vulnerable to impaired immune response. But the immune system’s response to amyloid plaques is as important to understanding the disease as the presence of amyloid plaques themselves.
Cynthia Lemere, PhD
Lemere’s lab recently found that a protein called complement C3 triggers an unhelpful immune response in patients with Alzheimer’s disease. The complement system, a cascade with many components including the central component C3, is the part of the body’s innate immune system to clear away pathogens. While complement C3 helps promote brain development early in life by pruning weak synapses, Lemere and her colleagues found this activity may be contributing to cognitive decline in aging brains.
“It surprised me that even when there is an abundance of plaques, the absence of complement C3, and its related fragments, can add protection against Alzheimer’s in genetically-engineered mice,” she says. “Complement interacts with the brain’s immune cells, called microglia and astrocytes, that help defend the brain against injury. Too much complement may tip the scales and cause elimination of synapses. Therefore, blocking specific parts of the complement cascade, perhaps using anti-complement antibodies for immunotherapy, might be protective against neurodegenerative diseases.”
Lemere says that like any other vaccine or antibody, Alzheimer’s immunotherapy has the best chance of working if given prior to the onset of the clinical symptoms of the disease.
“The earlier we go—perhaps starting an amyloid vaccine in adults in their 30s and 40s, because we now know that Alzheimer’s changes in the brain can start 15-20 or more years before the onset of cognitive decline—the better these antibodies will work. Blocking tau protein aggregation and adding an anti-inflammatory could only strengthen that protection.”
Her work signals other potential treatment avenues for a widely feared and increasingly prevalent disease with no cure.
“I have a lot of hope that we can prevent Alzheimer’s,” says Lemere. “In fact, at this point, I think prevention may be closer than a cure.”