Researchers at the University of Toronto's Tanz Center for Research in Neurodegenerative Diseases have used novel techniques to uncover which subtypes of brain cells express genetic material that produces tau, a key protein involved in the development of the neurodegenerative disease progressive supranuclear palsy (PSP).
, suggests that a two-pronged approach to treatment that targets two key mechanisms in disease development may be more effective than current methods.
One of the most common features of neurodegenerative diseases such as PSP and Alzheimer's disease is the accumulation of misfolded tau protein in neurons and their supporting cells, impairing the function of these cells.express the gene MAPT, which codes for tau. For decades, the dominant view has been that neurons express MAPT RNA, but glial cells do not.
The research team, which included collaborators in Australia and Dubai, examined brain tissue samples from three patients who had PSP and three who did not. Having access to these post-mortem patient samples—which Forrest describes as"the most generous gift anyone can give"—allowed the researchers to have a more complete and realistic view of the RNA expression in different brain cell types compared to using animal models or cell cultures.
"We've long had this suspicion, but now we've been able to get the evidence to demonstrate that this is the case," says Forrest."How and why tau accumulates in glia in PSP is not entirely clear, but our study highlights two novel mechanistic pathways for the cell-to-cell transmission of misfolded tau and accumulation in the brain, which is an exciting result."
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