Scientists at King's College London have described a previously unrecognised way that brain cells die, and found its fingerprints in the brains of people who had Alzheimer's disease and frontotemporal dementia. The mechanism, named karyoptosis, is a chain of chemical reactions set off by the build-up of toxic proteins inside neurons. Cells dying this way show a distinctive signature: the nucleus, which holds the cell's genetic material, shrivels and then breaks apart. The work, carried out with the UK Dementia Research Institute and funded in part by Alzheimer's Research UK, was published in Nature Communications.
The study applied computational algorithms to roughly 3,000 cells taken from the brains of 28 patients who had either frontotemporal dementia or terminal stage Alzheimer's disease, sorting them by the type of cell death they showed. In the frontal cortex of the Alzheimer's cases, 35 per cent of cells bore signs of karyoptosis, compared with 15 per cent in brains from healthy older people.
That gap matters because the existing explanations for neuron loss have never fully added up. Toxic protein accumulation is a hallmark of Alzheimer's, frontotemporal dementia and amyotrophic lateral sclerosis, yet known cell death pathways such as apoptosis do not account for all the neurons that disappear. Karyoptosis offers a candidate link between the proteins that pile up and the cells that ultimately die - and each chemical step in that chain is, in principle, something a drug could be designed to interrupt.
For now this is a description of what happens in brain tissue after death, identified through computational analysis rather than tested in living patients, and no treatment aimed at karyoptosis exists. The immediate value is in naming a target: researchers looking for ways to keep neurons alive now have a specific process to study and attempt to block.