Scientists discover mechanism for brain cell death in Alzheimer’s disease
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Alzheimer's Research UK
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On 25 June 2026
For decades, scientists have known that toxic proteins build up in the brains of people living with Alzheimer’s disease and frontotemporal dementia (FTD), but exactly how this leads to the death of brain cells has remained unclear. Now, researchers at King’s College London and the UK Dementia Research Institute have uncovered a new mechanism in Alzheimer’s disease and FTD that could help explain why. Their findings offer fresh hope for treatments that may slow disease progression and preserve brain function.
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.”
Where can I find the new research?
The findings were published in Nature Communications in a paper titled Karyoptosis mediates cell death and neurodegeneration upon proteotoxic stress.
Alzheimer’s Research UK and the Biotechnology and Biological Sciences Research Council International Partnership primarily funded the research, with additional support from the UK Medical Research Council and the UK Dementia Research Institute.
This news story was adapted from an article by King’s College London.
About the author
Alzheimer's Research UK
What are the chemicals that cause brains cell to degenerate and eventually leave people with forms of bad memory and dementia?
Hi Jean, thanks for your question. There isn’t a single chemical that causes brain cells to degenerate and lead to memory problems or dementia. Instead, different diseases that cause dementia involve a build-up of abnormal proteins and other changes in the brain that damage and eventually kill brain cells.
In Alzheimer’s disease, the two main proteins involved are amyloid-beta and tau. More information about these proteins here: https://www.alzheimersresearchuk.org/dementia-information/types-of-dementia/alzheimers-disease/
These protein changes are thought to trigger a series of harmful processes, including inflammation, reduced energy production, and damage to connections between brain cells. Over time, this leads to the loss of brain cells and shrinking of parts of the brain that are important for memory and thinking.
Because I’ve been breathing in particles out of cars for 40 years and tasting it for 10 years, will I get dementia? I want to get tested to see how bad it is.
Hi Cheryl, thanks for your comment.
For most of us, whether or not we develop dementia is due to a mixture of our age, genes, lifestyle, health and environment. There are some things we can control, and others that we can’t. Air pollution, including fumes from car exhausts, has been identified as a risk factor for dementia. More information here: https://www.alzheimersresearchuk.org/dementia-information/dementia-risk/air-pollution-and-dementia-risk/
The good news is that evidence suggests almost half of dementia cases worldwide could be prevented or delayed by addressing 14 ‘risk factors’. These include being physically active, staying socially connected, and managing existing health conditions such as high cholesterol or type two diabetes. To learn more about reducing your risk of dementia, visit here: https://www.alzheimersresearchuk.org/dementia-information/reducing-your-risk/
If you are concerned about your memory and thinking, the first person you should speak to is your GP. They can assess any memory concerns and refer you for further testing if necessary. They can also conduct a blood test to rule out any other causes of memory issues.
More information about getting a dementia diagnosis can be found here: https://www.alzheimersresearchuk.org/dementia-information/getting-a-dementia-diagnosis/
Thank you. Would like more information please.
Hi Constance, thanks for your comment. If you have any questions relating to dementia or this article, please feel free to contact the Dementia Research Infoline at infoline@alzheimersresearchuk.org or call 0300 111 5111.
My mother and elder sister both had Alzheimer’s and passed away. I’m 71 and getting forgetful. Am I going to get it? Are the odds against me?
Hi Anne, thank you for your comment. We are so sorry to hear about your family history of Alzheimer’s disease.
As the diseases that cause dementia are very common, it is not unheard of to have multiple family members affected by dementia. However, directly inherited dementia is very rare, accounting for around one in 100 cases. This is where multiple people in the same blood line across generations are affected the same disease (such as Alzheimer’s or frontotemporal dementia), often in their 40’s and 50’s. If this describes your family, you can talk to your GP about genetic counselling and testing.
Most dementia cases are caused by a mixture of factors including our age, genetics, lifestyle, and environment.
You can find out more about genes and dementia here: https://www.alzheimersresearchuk.org/dementia-information/genes-and-dementia/
In my position is there any medication or advice?
Hi Anne, thanks for your comment.
For most of us, whether or not we develop dementia is due to a mixture of our age, genes, lifestyle, health and environment. There are some things we can control, and others that we can’t.
The good news is that evidence suggests almost half of dementia cases worldwide could be prevented or delayed by addressing 14 ‘risk factors’. These include being physically active, staying socially connected, and managing existing health conditions such as high cholesterol or type two diabetes. To learn more about reducing your risk of dementia, visit here: https://www.alzheimersresearchuk.org/dementia-information/reducing-your-risk/
Try eating more healthy food and vegetables, try some low fat yoghurt, try some exercise. Don’t sit at home all day staring at walls or windows, don’t watch TV too much either, try to exercise your brain through doing some crosswords – even if you don’t get the right word to fit, put in what you make fit
Can I be a guinea pig as my odds on getting Alzheimer’s are high?
Hi Anne, thank you for your interest in taking part in dementia research studies. It’s people like you who will make finding a cure for dementia possible.
The best way to find out about this is through an NHS service called Join Dementia Research. You can find out more on our website: https://www.alzheimersresearchuk.org/research/getting-involved-in-research/
If you would prefer to talk to someone and sign up over the phone, you can give us a call on 0300 111 5111.
Reading the above clarifies a lot of changes that occur which I was not aware of. It helps tremendously with understanding the many changes that occur daily. Many thanks for all the important information.
What practical lifestyle steps can be taken to reduce the prospects of establishing these toxic processes, if any. Can the use of anaerobic exercise and combining support processes to conserve BDNF stimulated new neurons using such as tactile stimulation be recruited to help?
Hi David, thanks for your question. To find out more about reducing your risk of dementia, please visit here: https://www.alzheimersresearchuk.org/dementia-information/reducing-your-risk/
Is dementia developed from medication?
Hi Carol, thanks for your comment. For most of us, whether or not we develop dementia is due to a mixture of our age, genes, lifestyle, health and environment. There are some things we can control, and others that we can’t.
The good news is that evidence suggests almost half of dementia cases worldwide could be prevented or delayed by addressing 14 ‘risk factors’. These include being physically active, staying socially connected, and managing existing health conditions such as [ET1.1]high cholesterol or type two diabetes. To learn more about reducing your risk of dementia, visit here: https://www.alzheimersresearchuk.org/dementia-information/reducing-your-risk/
Hi Ron. Thank you for your comment.
This is a great question and one that researchers are actively exploring.
Dementia has likely existed throughout human history, although we have limited information about its prevalence in the distant past.
Age is the biggest risk factor for dementia. The older we are, the more likely we are to develop a disease like Alzheimer’s. While much of the increase in dementia cases today reflects the fact that people now are living longer, there is also evidence that a range of lifestyle, health and environmental factors can influence dementia risk. Factors such as physical inactivity, ultra processed diets, air pollution, smoking, excessive alcohol use, social isolation and increased prevalence of conditions like high blood pressure and diabetes have all been linked to an increased risk of dementia.
Understanding how these factors contribute to dementia risk remains an important area of ongoing research.