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Removing “zombie cells” improves symptoms of dementia

Researchers in Minnesota have found that the removal of a certain type of cell in the brain improves symptoms of dementia in mice. Senescent, or “zombie cells”, are cells in the brain which have entered a semi-dormant phase, part of the body’s natural defence against cancer. Cells that have several mutations which could cause uncontrolled growth, potentially leading to tumours, enter the senescent state, reducing the chance of tumour growth. Upon removal of these cells, researchers found symptoms of dementia in mice disappeared.

Researchers, writing in Nature, found that in mice with a genetic form of dementia, senescent cells accumulate in areas of the brain involved in memory and cognition (e.g. the hippocampus). Mice were genetically modified to produce a faulty version of the Tau protein. This cause the Tau protein to become hyperphosphorylated, which in turn results in the Tau proteins becoming insoluble, causing causes them to form large clumps of insoluble protein, called “tangles”. Tangles stop ordinary cell functions as they block the distribution of nutrients throughout the cell, hence the cells enter the semi-dormant, senescent state, to stop the spread of the Tau mutation. However, once thought to be harmless, these results are part of an ever-growing collection of evidence that over the last decade has linked senescent cells to Parkinson’s disease, diabetes, arthritis and heart disease. Although it is not exactly clear why the presence of senescent cells cause such issues, previous work had indicated that they could be caused by the cells secreting inflammatory chemicals, and by causing neighbouring cells to become senescent too.

Senescent, or “zombie cells” are cells in the brain which have entered a semi-dormant phase, part of the body’s natural defence against cancer

The researchers developed a genetically modified enzyme to remove the senescent cells, which when applied to mice with dementia, the outward symptoms to disappeared entirely. The mice were able to develop memories normally and inflammation in the brain decreased. Furthermore, the brain retained a normal mass and tau proteins tangles did not continue to develop. However, whether or not the results will translate into human brains remains to be seen and will require further testing. For instance, older people often have many harmless cells that appear very similar to senescent cells, so developing a drug that is able to differentiate between harmful senescent cells and others is highly important. Furthermore, it is yet to be seen if the enzyme is able to enter the human brain, The removal of the senescent cells also raises further questions – will the brain shrink in overall size, or whether new cells would grow to replace those removed.

According to the Alzheimer’s Society, there hasn’t been a new drug for treating dementia for 15 years, so these results show promising progress towards understanding and developing treatments for suffers of dementia and Alzheimer’s. Over half a million people in the UK alone are currently diagnosed with dementia, and there are many more with the disease but no diagnosis. It is predicted that by 2025 this figure will have doubled, and by 2050 quadrupled to two million diagnosed sufferers. Dementia and Alzheimer’s disease causes problems remembering, thinking and speaking. Common symptoms include forgetting recent events and faces, getting lost, difficulty expressing themselves, and finding it hard to make simple decisions. This can be highly distressing for both sufferers and loved ones. A cure for dementia would allow loved ones to age more peacefully and with the dignity they deserve.

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