Researchers have identified a previously unknown mechanism called karyoptosis that appears to drive the death of brain cells in Alzheimer's disease and frontotemporal dementia. The discovery, based on analysis of human brain tissue, points to a potential new target for treatments aimed at slowing neuron loss.
Scientists at King's College London, working with the UK Dementia Research Institute, examined 3,000 brain cells from 28 individuals with either frontotemporal dementia or advanced Alzheimer's. They detected signs of karyoptosis in 35 percent of cells from the frontal cortex of Alzheimer's patients, compared with 15 percent in healthy older adults.
Karyoptosis begins when toxic proteins accumulate inside neurons. This buildup destabilizes the nuclear membrane, causing the cell's nucleus to shrink and eventually break apart. Laboratory tests on rat neurons showed that blocking the interaction between p38 MAP kinase and LaminB1 reduced markers of this process.
"This study is the culmination of a 10-year journey at King's," said Dr. Manolis Fanto, Reader in Functional Genomics at the Institute of Psychiatry, Psychology and Neuroscience. Dr. Rebecca Casterton, first author and Senior Researcher at the UK Dementia Research Institute, added that the work lays out a road map for how karyoptosis operates.
The findings were published in Nature Communications. Alzheimer's Research UK and the Biotechnology and Biological Sciences Research Council provided primary funding.
