Somatic Mutations

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.