According to figures provided by Deutsche Alzheimer-Gesellschaft, there are about one million Germans currently living with Alzheimer’s disease. And the number is rising. After all, with demographic change in progress, there is also an increase in the number of those at risk of developing Alzheimer’s disease, a particular form of dementia in which patients’ nerve tissue is systematically destroyed.
This leaves Alzheimer’s sufferers less and less able to manage their daily lives on their own. They tend to lose their way and have memory problems, sometimes even failing to recognize their closest relatives.
“A few years ago, you would still be laughed at in the research community if you asserted that Alzheimer’s disease had anything to do with inflammation,” says Professor Frank Heppner. Heppner, a physician and medical researcher, is the head of the neuropathology department at Charité, in Berlin’s Mitte district. He is convinced that Alzheimer’s disease is associated with inflammatory processes taking place in the brain. “For a long time, the only disease that people associated with inflammatory responses in the brain was multiple sclerosis. Today, we know that chronic processes of inflammation, some of them very subtle, are very likely involved in most neurodegenerative disorders,” Heppner says.
This category includes not only Alzheimer’s disease, but also Parkinson’s disease – diseases in which nerve cells are destroyed. If nerve tissue is destroyed, patients experience symptoms such as shaking, or they may lose the ability to move certain parts of the body. The root causes of disease are not always clear, but processes involving the body’s own immune cells probably always play a role. “Neuroimmunology is an exciting new field of research,” says Heppner.
Within the scope of various working groups, the researchers at Charité are investigating inflammatory processes in various diseases of the brain. The research involves scientists from the NeuroCure cluster of excellence and the transregional collaborative research center TRR43 with University Medical Center Göttingen.Their goal is to better understand the mechanisms that give rise to these diseases, in hopes of finding commonalities between them.
In Alzheimer’s Patients, the “Brain’s Police Force” Does Not Work Properly
Inflammation varies from organ to organ; just as a liver cell and a brain cell are very different from each other, inflammatory responses in the various tissue types and organs also vary. “Liver cells that have been destroyed regenerate. That’s not the case in the brain, where cells regenerate only to a very limited extent,” Heppner explains. He adds that this is why it is important for immune cells in the brain to proceed differently – gently, that is.
These careful agents in the brain are a specialized type of cells called microglia, which are a kind of phagocyte, the cells tasked with “eating” harmful substances in the body. With a tentacled shape reminiscent of an octopus, they are located throughout the brain, constantly feeling around them for potential pathogens. “You might think of the microglia as the brain’s police force,” Heppner says. These phagocytes are hugely important, as their sheer quantity illustrates: Microglia make up eight to 15 percent of the brain’s mass. But what if they don’t behave the way they are supposed to? “Our research provides clear evidence that the behavior of microglia is substantially connected with Alzheimer’s disease,” Heppner says.
In the brains of people with Alzheimer’s disease, large volumes of certain proteins are produced, some of them forming blob-like deposits. These blobs should be broken down by the microglia, but a study of mice showed that the macrophages do not respond appropriately to the disruptive proteins. “The Alzheimer’s environment is evidently bad for microglia. They do not break down the proteins, but instead start to produce inflammatory substances called interleukins,” Heppner says.
The Charité researchers suspect that these substances have a negative effect on the progress of the disease. In studies of mice with Alzheimer’s disease, Heppner’s working group blocked the inflammatory substances. The result: The mice given this treatment were significantly healthier than those in which the interleukins were not blocked.
The scientists now also plan to adopt the same approach to treating the disease in humans. “There is already one drug that specifically counteracts these inflammatory substances. We hope to be able to test it soon in a clinical trial involving Alzheimer’s patients,” says Heppner. He cautions against excessive optimism, however. “If someone is already suffering from the late stages of Alzheimer’s disease, the changes cannot be reversed,” he points out.
Still, Heppner hopes that he and his colleagues will succeed in blocking inflammation in the brains of Alzheimer’s patients, giving them a few more years of life with as little disruption from dementia as possible. “We can’t cure Alzheimer’s disease. But slowing the progress of the disease – I think that’s definitely realistic,” he says.