A research team at the University of Sheffield is exploring the differing effects of amyloid beta protein forms on nerve cells, aiming to identify methods for protecting the brain in the early stages of Alzheimer’s disease. The study focuses on understanding why one form, amyloid beta 42, is particularly harmful compared to another, amyloid beta 40, which is considered less damaging in healthy brains.
Emma Garland, a Research Associate, and her colleagues, led by Senior Research Fellow Dr Suman De, are using human stem cells to create nerve cells in the laboratory. These cells are then exposed to different forms and amounts of amyloid beta to observe the impact. The research also investigates the role of the APOE gene, comparing cells with the higher-risk APOE4 version against those with the common APOE3 version, to see how genetic background influences nerve cell response.
The team is also analysing donated human brain tissue from individuals with and without Alzheimer's disease. Using immunohistochemistry, they can identify and quantify specific proteins within plaques, confirming that disease-related plaques are predominantly composed of amyloid beta 42.
Initial findings suggest a potentially protective role for amyloid beta 40. The research indicates that a higher ratio of amyloid beta 42 to amyloid beta 40 significantly increases toxicity to nerve cells. Crucially, increasing levels of amyloid beta 40 were found to reduce the toxic effects of amyloid beta 42.
"Our data shows that increasing levels of amyloid beta 40 reduces the toxic effects caused by amyloid beta 42, opening an exciting new route for potential therapies," stated Emma Garland. This discovery could lead to treatments that prevent nerve cell loss before widespread brain damage occurs, addressing a current lack of preventative therapies for Alzheimer's.
The long-term goal is to re-balance amyloid beta protein levels, potentially forming the basis for early-stage preventative treatments. The stem cell models and techniques developed could also be applied to research into other neurodegenerative diseases, aiming to improve the lives of those affected.
The research team includes postdoctoral researcher Agnieszka Urbanek and PhD student Harry Baker, working within Dr Suman De’s research group. The project is funded by a UKRI Future Leaders Fellowship.
