Alzheimer’s disease is traditionally thought to be caused by the accumulation of abnormal protein in the brain. Get rid of the protein, the thought goes, and you reduce the damage. But what if Alzheimer’s disease is actually an autoimmune disease? For more than 20 years, Toronto neurologist and pharmacist Donald Weaver has sought a different explanation for neurodegenerative disease in hopes of finding new ways to treat and prevent it. His unconventional case has now won a major award. On Wednesday, to Dr. Weaver will be awarded the $ 400,000 USD Oscar Fisher Award. The award, given through the University of Texas at San Antonio (UTSA), is given to researchers to broaden their understanding of Alzheimer’s disease, which has long confused those seeking treatment. “What it gives us is external validation and external support and the belief that our approach has value, and indeed, can have value that leads to alternative therapies for Alzheimer’s disease,” says Dr. Weaver, director of the Krembil Brain Institute at the University of Toronto Health. Network. More than 115 years after the first patient was recorded, the causes of Alzheimer’s disease are still not well understood. For years, the predominant hypothesis was the amyloid hypothesis – that the main cause is the accumulation of beta amyloid, which are sticky fragments of protein that form toxic clusters or plaques. However, amid the failures of many amyloid-targeting drugs, the call for alternative explanations for the disease has become stronger. More recently, Genentech, a member of the Roche Group, announced this month that testing of the antimyloid drug crenezumab did not yield a statistically significant clinical benefit. Instead of seeing beta amyloid as an unwanted protein, Dr. Weaver suggests that it is actually a normal part of the innate immune system in the brain and plays a variety of roles, including as a messenger and as a killer of bacteria. “Anything that triggers an immune response, whether it’s an infection, trauma or exposure to harmful substances, activates cells in the brain to release beta amyloid,” he explains. The problem arises when beta amyloid confuses healthy brain cells for bacteria, he says. “The end result is that – oops! “It accidentally starts killing brain cells.” The damage does not stop there, he explains. The fragments created when beta amyloid destroys brain cells continue to cause the continuous release of beta amyloid, which in turn can accidentally kill more brain cells, he says. “This is how a chronic disease eventually becomes over many, many, many years.” Dr. Weaver says genetics may play a role in determining why some people develop Alzheimer’s disease, but others do not, as the former may produce larger amounts of beta amyloid in response to the same immune system triggers. But he says there is an argument that everyone would eventually develop Alzheimer’s disease if they were to live long enough. Biological variability may explain why it progresses faster in some than others, he suggests. Based on his hypothesis, Dr. Weaver believes that it is possible to treat Alzheimer’s disease by utilizing the natural way of controlling the body’s immune system. He and his team have tested about 1,300 chemicals in the brain for their ability to suppress the innate immune system and have identified some chemicals that they believe could be developed as potential therapies. His case may also have an impact on the prevention of Alzheimer’s disease, he adds. “If we accept the fact that Alzheimer’s disease is an immune-based disease that has certain stimuli, then I think we need to go back and re-examine the risk factors,” he says. For example, it highlights the need to better understand how different types of air pollution affect the brain and to find ways to prevent head trauma. The same mechanism of the immune system may also apply to other diseases, such as Parkinson’s disease or other forms of dementia, says Dr. Weaver. “This is a broad conceptual basis that can be extended to other disorders.” Any of the explanations for the disease suggested by the 10 winners of this year’s Oskar Fischer Award could be right or wrong, says Dr. Jenny Hsieh, director of the UTSA Brain Consortium. But the key is to give researchers the opportunity to pursue ideas that are out of context, he says. “We just need people to be able to work on different ideas and incorporate them, because the essence is all the current approaches to Alzheimer’s disease. [are] not working.” The Morning and Afternoon Newsletters are compiled by Globe editors, giving you a brief overview of the day’s most important headlines. Register today.
