Cell death in dementia has long posed a frustrating problem. Toxic proteins pile up inside neurons in Alzheimer’s disease and frontotemporal dementia, but the exact route from that buildup to the loss of brain cells has remained hazy. A study from King’s College London and the UK Dementia Research Institute now argues that one missing piece may be a newly characterized process called karyoptosis, in which a neuron’s nucleus shrivels and breaks down before the cell dies. The work, published in Nature Communications, links that process to proteotoxic stress, the burden created when damaged or misfolded proteins accumulate and the cell’s cleanup machinery can no longer keep pace. In post-mortem brain tissue, the team found markers of karyoptosis in a substantial share of neurons from people with Alzheimer’s disease and frontotemporal lobar degeneration, suggesting this is not a rare quirk of the lab but a feature of human disease. “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 …