From UF Center for Translational Research in Neurodegenerative Disease
New preclinical research led by UF neuroscientists shows that tau proteins, considered a hallmark of Alzheimer’s disease pathology, build up in brain cells of mice and continue to be cleared. The novel finding published in the journal Acta Neuropathologica indicates that reversing pathological tau formations could be possible.
Understanding the cellular processes behind the turnover could help guide the development of future therapeutic strategies aimed at such a reverse, the researchers reported.
In the new study, investigators engineered non-infectious viruses and introduced them to thin sections of brain tissue from mice to track old and new tau protein in different colors and follow it over several weeks. The researchers used microscopy to capture images of the living brain tissue every few days to track the new and old tau protein clumps and discovered that the old tau protein clumps were gradually being cleared away.
“We hope that future research will lead to further understanding of how the cells are able to clear these tau clumps and whether this helps to make the cell healthy,” said first author Cara Croft, Ph.D., a postdoctoral associate in the lab of Todd Golde, M.D., Ph.D., the study’s senior author and director of UF’s McKnight Brain Institute.
“If this clearance process is beneficial, then it is likely that we can start to test whether drugs or other methods are able to speed up this process and may form a new avenue for treatment of Alzheimer’s disease or other diseases that involve changes in tau,” Croft said.
Croft provides further detail: “We have been studying one of the proteins – tau which becomes sticky and clumps together in Alzheimer’s disease. Tau buildup in humans with Alzheimer’s disease is known to be linked to cognitive decline and brain cell loss which is believed to drive the symptoms that is seen in these patients. The typical thinking in the field was that tau builds up and sort of creates a permanent “tombstone” like structure in the brain cell. However, we have found that the tau clumps in the cell are actually constantly turning over and non-clumped tau replaces the clumped tau. Though this turnover slows down over time, the fact that the clumps turnover indicates it may be possible to actually reverse long-standing tau pathology. This could then perhaps slow down or halt the progression of Alzheimer’s disease and other neurodegenerative diseases in which tau plays a role.”
“To study this, we engineered non-infectious viruses that enable us to track old and new tau protein in different colors and follow it over several weeks. These viruses were then introduced to thin sections of mouse brain tissue that we can keep alive for a long time in petri dishes. We used microscopy to capture images of the living brain tissue every few days to track the new and old tau protein clumps and were able to see the old protein clumps gradually being cleared away.”
“As this has never been shown before, we hope that ourselves and others will be able to start to understand how the cells are able to clear these tau clumps and whether this helps to make the cell healthy. If this clearance process is beneficial, then it is likely that we can start to test whether drugs or other methods are able to speed up this process and may form a new avenue for treatment Alzheimer’s disease or other diseases that involve changes in tau.”