New mechanism found for neuronal death in Alzheimer's and frontotemporal dementia
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Markers of a new mechanism for cell death, called karyoptosis, have been found in the brains of patients with Alzheimer's disease and frontotemporal dementia (FTD).
In many neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS), Alzheimer's and FTD, toxic levels of proteins accumulate inside neurons, which subsequently die. While there are other known forms of cell death, such as apoptosis, they do not account for all neuronal loss in neurodegenerative disease.
New research from King's College London in collaboration with the UK Dementia Research Institute, reveals that karyoptosis may provide a key link between toxic protein accumulation and neuron death.
Karyoptosis is the set of chemical reactions triggered by toxic protein accumulation that ultimately causes cell death. When a cell dies by karyoptosis, the nucleus—the part of the cell that contains the genetic information—shrivels before disintegrating.
The study, published in Nature Communications, used computational algorithms to identify key types of cell death in 3,000 cells from the brains of 28 patients with either FTD or terminal-stage Alzheimer's disease. Some 35% of cells from the frontal cortex of patients with Alzheimer's showed signs of karyoptosis, compared with only 15% in healthy older controls.
"This study is the culmination of a 10-year journey at King's, from when we first identified karyoptosis in a relatively rare disease to discovering that it is a common feature of dementias that affect millions of people."
The study identified a key mechanism controlling karyoptosis that could be triggered by causing proteins in neurons to clump together, a common feature of neurodegenerative disease. In this pathway, toxic levels of protein accumulation cause the outside of the nucleus to become unstable, leading it to shrivel and disintegrate.
By targeting proteins that act as "switches" in this pathway, called kinases, researchers were able to reduce levels of karyoptosis markers in rat neurons in a dish. Specifically, they showed that the interaction between one particular kinase, called p38 MAP kinase, and another protein, LaminB1, is a key target for blocking or slowing nuclear disintegration.
This pathway has the potential to provide new therapeutic targets for slowing or preventing cell death by karyoptosis in dementia. Future work will focus on selectively targeting this protein-kinase interaction to produce viable treatment targets in humans.
"By specifically targeting the interaction between p38 MAP kinase and LaminB1, we may slow down the process of cell death, buying time for more pinpointed therapies against specific neurodegenerative diseases," said Dr. Manolis Fanto, reader of functional genomics, Institute of Psychiatry, Psychology and Neuroscience, King's College London.
"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 that can coordinate cell death in brain cells. We have started to lay out the roadmap of how karyoptosis works, and I'm excited to see future breakthroughs this may drive in the dementia research community and beyond," added Dr. Rebecca Casterton, senior researcher at the UK Dementia Research Institute at King's and first author on the paper.
"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 toward 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," concludes Dr. Sara Rodrigues, senior research manager at Alzheimer's Research UK.
Publication details
Karyoptosis mediates cell death and neurodegeneration upon proteotoxic stress, Nature Communications (2026). DOI: 10.1038/s41467-026-73802-w
Journal information: Nature Communications
Key medical concepts
Alzheimer's DiseaseFrontotemporal Dementiap38 Mitogen-Activated Protein Kinases
Clinical categories
Neurology Provided by King's College London Who's behind this story?
Sadie Harley
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Master's in physics with research experience. Long-time science news enthusiast. Plays key role in Science X's editorial success. Full profile →
Citation: New mechanism found for neuronal death in Alzheimer's and frontotemporal dementia (2026, June 25) retrieved 25 June 2026 from https://medicalxpress.com/news/2026-06-mechanism-neuronal-death-alzheimer-frontotemporal.html This document is subject to copyright. Apart from any fair dealing for the purpose of private study or research, no part may be reproduced without the written permission. The content is provided for information purposes only.