Natural history of disease in the YAC128 mouse reveals a discrete signature of pathology in Huntington disease

► Brains of aging YAC128 mice show features consistent with human Huntington disease. ► Regions of specific sparing as well as atrophy are observed in aging YAC128 mice. ► Classification trees identify regions that discriminate YAC128 from wild type mice. ► Progressive cortical pathology in the YAC128 mice restricted to projection layers.