‘Zombie’ cell elimination offers Alzheimer’s treatment hope

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Eliminating so-called “zombie” cells in the brain has been shown to reduce cognitive decline in mice.

New research, published in the journal Nature, reveals a link between neurodegeneration and the accumulation of senescent cells.

The findings could aid developments in the diagnosis and treatment of conditions such as Alzheimer’s disease, experts said.

Senescent or “zombie” cells are defective cells which can no longer reproduce or perform their normal functions, but cannot die.

US researchers, from the Mayo Clinic in Minnesota, found they gather in certain brain cells in mice before the loss of cognitive ability.

Senescent cells, shown in green, can send inflammatory signals to neighbouring cells (Mayo Clinic/ PA)
Senescent cells, shown in green, can send inflammatory signals to neighbouring cells (Mayo Clinic/PA)

In the new study, they imitated the features of Alzheimer’s in the animals.

The mice were genetically modified to have a “suicide gene”, activated by a drug, which eliminates the senescent cells.

The drug was used throughout the life of the mouse, reducing the build-up of tau, a damaging chemical linked to Alzheimer’s and degeneration of the brain.

Lead author Tyler Bussian said: “When senescent cells were removed, we found that the diseased animals retained the ability to form memories, eliminated signs of inflammation, did not develop neurofibrillary tangles, and had maintained normal brain mass.”

They also identified two brain cell types, called microglia and astrcytes, as those which become senescent.

These cell types help support neuronal health and signalling, the researchers said, and it “makes sense” that their decline would affect the function of the brain.

They believe the cells may provide a target for the treatment of cognitive diseases, but warn further research is needed to establish whether the findings can be replicated in humans.

Senior author Dr Darren Baker said: “Clearly, this same approach cannot be applied clinically, so we are starting to treat animals after disease establishment and working on new models to examine the specific molecular alterations that occur in the affected cells.”

Dr James Pickett, head of research at Alzheimer’s Society, said: “There hasn’t been a new dementia drug in 15 years so it’s exciting to see the results of this promising study in mice.

“However, there are several barriers to overcome before we can say if this is a safe, effective treatment in people.

“For example, we don’t know if this drug is actually able to enter the brain, and older people often have lots of harmless brain cells that look like the senescent ‘zombie’ cells this drug targets, so any treatment would have to be good at telling the two apart.”

Dr Rosa Sancho, head of research at Alzheimer’s Research UK, said: “As this study cleared toxicity using genetic techniques in mice, further efforts are needed to explore how this approach could be translated into a treatment that could be tested in people.

“There are many hurdles to overcome in developing treatments for neurodegenerative diseases, targeting these cell types could be a promising approach but is still some way off benefiting people living with dementia.”

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