New research could be key in unlocking better treatment for Alzheimer’s by Erin Kayata October 11, 2023 Share Mastodon Facebook LinkedIn Twitter Photo by Ruby Wallau/Northeastern University There’s still many unknowns surrounding Alzheimer’s disease, including just how it progresses. But a Northeastern professor is planning on studying the molecular mechanisms of the disease in hopes of understanding how it spreads, which could open avenues for better treatment. Professor Lee Makowski, chair of Northeastern University’s Bioengineering Department, received a grant from the NIH to study the changes to the molecular structure of the amyloid plaques and neurofibrillary tangles that grow throughout the brain over the course of the disease. Lee Makowski, bioengineering department chair, secured a grant to investigate alterations in the molecular structure of Alzheimer’s disease-related amyloid plaques and neurofibrillary tangles. Photo by Matthew Modoono/Northeastern University “What I’m hoping we’ll do is really focus on what the molecular processes are that drive the progression of the disease,” he said. “We’re trying to watch the progression of these plaques and tangles during the development of the disease and as it moves across the different areas of the brain.” The plaques that cause Alzheimer’s are a buildup of proteins and peptides that start in one place and grow through the brain over a period of years, according to Makowski, leading to the destruction of brain synapses, which leads to the symptoms people associate with Alzheimer’s. “We know a huge amount about Alzheimer’s,” Makowski said. “The government has been putting billions of dollars into Alzheimer’s research for many years, because we know that as the population ages, there’ll be a great deal more people with Alzheimer’s. But connecting the dots has proven to be incredibly difficult.” The National Institute of Health awarded Makowski over $2 million for this study. Understanding how the molecular structure changes as the disease progresses could aid in developing new treatments. If researchers know the molecular changes that lead to plaque growth, they can target them through treatment and cause the growth to slow or stop. Makowski and his team will work with Massachusetts General Hospital to get brain tissue from patients who died with Alzheimer’s. The study will examine people who died during various stages of the disease, from early to end, in order to get a sense of the full progression of Alzheimer’s. They’ll also examine tissue from different areas of the brain. To do so, Makowski and his team will use X-ray scanning microdiffraction to examine the molecular structure of the plaques and tangles and whether they change throughout the course of the disease. This method also allows them to see how the fibrils interact with different protein structures in the brain and whether these interactions aid in progression. “The whole idea here is to find out if there are transitions in the fibril structure during the progression or is the fibral structure more or less conserved during progression, which would suggest it had migrated and replicated somewhat,” he said. “If we can identify which of those interactions are important, we may be able to find compounds that can block those interactions and potentially slow down the progression.” Over the last year, there have already been several therapeutics approved for slowing down the progression of Alzheimer’s by about 20% to 30%. This research, if successful, could help in the development of treatments that could slow the disease even further if researchers can figure out how to disrupt the interactions causing the plaques to grow. “It would be great if we could identify a couple of interactions that are important to progression,” Makowski said. “If we can do that, I feel like we will have moved the needle a little bit forward and increased our understanding of what the fundamental drivers of Alzheimer’s are.” Erin Kayata is a Northeastern Global News reporter. Email her at firstname.lastname@example.org. Follow her on X/Twitter @erin_kayata.