Discovery of karyoptosis opens new therapeutic targets for Alzheimer's and frontotemporal dementia

Markers of a new mechanism for cell death, called karyoptosis, have been found in 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, and funded in part by Alzheimer's Research UK, 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, which ultimately cause 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 3000 cells from brains of 28 patients with either FTD or terminal stage Alzheimer's disease. 35 per cent of cells from the frontal cortex of patients with Alzheimer's showed signs of karyoptosis, compared to only 15 per cent in healthy aged controls.