Scientists Discover Mechanism For Brain Cell Death In Alzheimer’s Disease
Scientists at King’s College London and the UK Dementia Research Institute have made a significant advance in understanding how Alzheimer’s disease and frontotemporal dementia (FTD) damage the brain.
While it has long been established that toxic proteins accumulate in the brains of those living with both conditions, the precise mechanism by which this leads to the destruction of brain cells has, until now, remained poorly understood. Researchers have identified a new biological pathway that may finally explain this process — a discovery that carries considerable promise for the development of therapies capable of slowing disease progression and protecting brain function in those affected.
The research project, part-funded by Alzheimer’s Research UK, suggests a process known as ‘karyoptosis’ may play an important role in the progressive loss of brain cells seen in dementia.
Dr Sara Rodrigues, Senior Research Manager at Alzheimer’s Research UK, says: “For decades, we’ve known that toxic proteins build up in Alzheimer’s disease and frontotemporal dementia, but exactly how they lead to the loss of brain cells has remained unclear.
“The identification of karyoptosis is a crucial step towards finding targets for treatments that could stop or slow cell loss. It could help widen the window for therapies that tackle the underlying causes of disease, bringing us closer to a cure for dementia. This is why Alzheimer’s Research UK funds and supports research.”
What does the new research tell us about Alzheimer’s and FTD?
Unlike other forms of cell death, karyoptosis causes the cell’s nucleus – the control centre that contains its genetic material – to shrink and break apart before the cell dies.
After examining around 3,000 brain cells from 28 patients, researchers found signs of karyoptosis in more than one-third of cells in the frontal cortex of people with Alzheimer’s disease. Meanwhile, just 15 per cent of cells in healthy older brains showed signs of karyoptosis.
Further analysis also showed that targeting certain proteins that act as molecular ‘switches’, called kinases, reduced signs of karyoptosis in rat brain cells. In particular, the researchers noted that an interaction between a protein called p38 MAP kinase and another called LaminB1, may be key in blocking damage to the cell’s nucleus.
This highlights a potential way to slow the breakdown of brain cells and could offer new targets for treatments aimed at slowing brain cell loss in humans.
Dr Manolis Fanto, Reader in Functional Genomics, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, also says: “Our study is important for the understanding of dementia because it clarifies that there are multiple ways in which neurons die and the one specifically characterised by us, karyoptosis, was entirely unknown before. This information draws a new picture of the pathways that must be acted upon to keep the brain cells alive in dementia.”
Dr Rebecca Casterton, Senior Researcher at the UK Dementia Research Institute at King’s College London and researcher on the project, also says: “The death and loss of cells in the brain drives many symptoms experienced by people living with dementia.
“Our study uncovers a new series of chemical events which can coordinate cell death in brain cells. We have started to lay out the road map of how karyoptosis works, and I’m excited to see future breakthroughs this may drive in the dementia research community and beyond.”
