WorldCare Consortium™ member Mayo Clinic finds zombie cells in brains of mice precede neurodegenerative disease

08:00 24 September in Health, Medicine

Research from WorldCare Consortium™ member Mayo Clinic has found that prior to cognitive loss, “zombie” cells (also referred to as senescent cells) collect in certain brain cells. Researchers at the hospital were able to decrease tau protein accumulation, death of neurons and memory loss by preventing the buildup of zombie cells.

Zombie cells no longer divide but also do not die. They cannot perform normal cellular functions and tend to accumulate with age, with previous research from the Mayo Clinic team finding that a compound intended to eliminate senescent cells in mice led to longer life and a decrease in fat, muscle, and kidney tissue inflammation for the animals.

tau protein in neurons

This most recent study, intended to look at the role of zombie cells in neurodegenerative disease, involved experimentation with two ways of eliminating zombie cells in mouse models. One way involved a genetically engineered mouse who produced tangles of tau proteins in neurons, imitating the pathology of Alzheimer’s disease. This mouse was then engineered so that it could eliminate zombie cells after introduction of a certain chemical trigger. After the zombie cells were eliminated, the mice “retained the ability to form memories, eliminated signs of inflammation, did not develop neurofibrillary tangles, and had maintained normal brain mass,” stated Tyler Bussian of WorldCare Consortium™ member Mayo Clinic, first author of the new study.

The second method involved an experimental anticancer drug called navitoclax. It was discovered that the drug is also able to work as a senolytic agent, eliminating zombie cells from the animals’ brains and controlling the buildup of tau proteins. Also discovered was the fact that specific neurons becoming senescent didn’t lead to tau protein accumulation, but two other kinds of zombie cells, astrocytes and microglia, were the types of cells that became senescent.

As a result of this study, a causal link between zombie cells and the onset of neurodegenerative disease was found that had not previously been established. “We had no idea whether senescent cells actively contributed to disease pathology in the brain, and to find that it’s the astrocytes and microglia that are prone to senescence is somewhat of a surprise, as well,” stated Dr. Darren Baker, PhD, a Mayo Clinic molecular biologist and senior author of the paper.

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Journal Reference: Tyler J. Bussian, Asef Aziz, Charlton F. Meyer, Barbara L. Swenson, Jan M. van Deursen, Darren J. Baker. Clearance of senescent glial cells prevents tau-dependent pathology and cognitive declineNature, 2018; DOI: 10.1038/s41586-018-0543-y

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