Somatic genomic changes in single Alzheimer's disease neurons

Dementia in Alzheimer’s disease correlates with progressive neurodegeneration, but the precise causes of neuronal dysfunction remain unclear. This study analyzed single-cell whole-genome sequencing of 319 neurons from Alzheimer’s patients and controls, revealing increased somatic DNA mutations in affected neurons with distinct molecular signatures. While normal neurons accumulate mutations via age-related “clock-like” patterns, Alzheimer’s neurons exhibit additional oxidative DNA damage. These mutations affect coding regions and likely disrupt neuronal function, suggesting that genomic damage contributes to disease progression and neuronal impairment.