Undergrad Helps Study Connection Between Proteins, Dementia
By Julia Gavin
Devastating dementia-like symptoms are affecting younger patients according to recent studies, especially athletes, soldiers and others who have experienced brain trauma. Chronic Traumatic Encephalopathy (CTE), a progressive degenerative brain disease caused by repetitive trauma has the attention of athletes, the government and scientists, including research students on campus.
Ph.D student Brian Patuto is researching CTE as part of his interest in neuron regeneration. Andrew Sanginario, a biotechnology major from Boylston, had Patuto as a teaching assistant in his freshman year and made an impression with his class work. When Patuto had the opportunity, he brought Sanginario into the lab through the Honors Scholar Co-op program a few months later. They spent the summer studying brains that experienced repetitive brain trauma related to CTE and a protein called tau that may lead scientists to answers. With age, tau proteins form clumps between brain cells which prevent neurons from communicating with one another. The cells die, causing damage to the sufferer’s memory, physical functions, speech, judgment and other vital physical and mental abilities.
“We don’t think twice if a great-grandparent is in this state, but it’s the younger athletes and soldiers whose lives have deteriorated quickly due to head trauma who have caught national attention,” says Sanginario.
Patuto agrees that recent headlines have brought more attention to the competitive field of dementia research.
“No one’s arguing that the link between repeated trauma, tau and these dementia-like symptoms doesn't exist, but we don’t understand it fully,” says Patuto. “Key people, especially in the National Football League, want to figure it out and hopefully head off the damage. But we can’t effectively diagnose CTE early enough to help sufferers yet.”
Patuto’s research includes looking for patterns of tau proteins in the brains of deceased people who had repeated concussions and searching for other, more easily diagnosable clues to the disease’s path.
Sanginario assisted in the process’ first steps by prepping brain tissue for microscopy and incidentally troubleshooting protocols for Patuto’s research. They examined several brains in different stages of CTE to track tau’s presence and relationship to the disease’s progression.
“Each brain section was dehydrated in increasing amounts of alcohol, solidified in paraffin wax, sliced and loaded on to microscope slides after an alcohol bath,” says Sanginario. “Once dried, the slides of brain tissue were stained with different dyes in order to see the tau protein under a microscope. In the affected brains, the tau clumps were large and numerous and the axons that usually linked brain cells ended abruptly, like bridges to nowhere.”
In addition to giving Sanginario more hands-on lab time than many young scientists have in the field, the process helped him practice the patience, logic and creativity required for research. When a standard approach to the alcohol bath process wasn’t working, Patuto put his student to work finding an alternative. See some of the process in this lab video
“The tissue was almost pruning in the alcohol bath, like your fingertips when swimming, which made it difficult to examine on the slide. We really didn’t know why,” says Patuto. “Andrew thought it through, found some potential reasons and solutions from other research and kept trying them until he found the right balance of alcohol in the bath and the right liquid temperature to make it work.”
Patuto says that Sanginario’s logical thinking and willingness to try different approaches made trusting an assistant with this important research easy.
“If you can’t figure out why something is broken, you can’t fix it and that can burn months of time if you’re not willing to adapt,” says Patuto. “Andrew gets that.”
Sanginario didn’t expect to be conducting brain research just a few semesters into college. He’s always been interested in science, though, and the project’s connection to athletics intrigued the sports fan.
The samples came from the Boston University Center for the Study of Chronic Traumatic Encephalopathy, which accepts donated brains and other tissues for use in research. While anonymity is important, it is known that professional athletes and soldiers have donated their remains to the bank for CTE research. Lowell native and boxing icon Micky Ward is working with the organization to help their studies and will donate
his brain and spinal cord upon his death. Prof. Garth Hall, Patuto’s supervisor, is a co-author of a recent study published by the bank.
“Handling the brain tissue and understanding that it belonged to a person took a few days to get used to,” says Sanginario.
Sanginario plans to continue assisting Patuto in the research. In the spring, they will work with spinal fluid, brain tissues and homogenate and attempt to express tau in human cell lines. By watching the damage made to the cells, they hope to see the relationship between tau secretion and neuron degeneration.
“Studying and treating CTE is difficult because by the time the patient realizes there is a problem, they’re often in an advanced stage of the disease, meaning they have real dementia and significant damage has already been done,” says Patuto. “Between lacking early-stage human subjects and the difficulty in imaging the brain trauma, this research is very difficult Better understanding the impact of tau and finding other ways to diagnose CTE might help the process along.”
While Sanginario isn’t sure which research field he will pursue, he’s excited to help Patuto with this research through his co-op. The two have become fast friends and Patuto helps Sanginario navigate college decisions.
“Brian’s been an excellent mentor,” says Sanginario. “I’ve learned a lot and my co-op opportunity has been really rewarding.”