C6 and Alzheimer disease: As previously reported [41], 3xTg-AD mice at this age showed a marked reduction in spine density compared to WT mice; in contrast, the overall spine density in 3xTg-AD C6−/− was comparable to that in WT mice; comparison of C6-deficient and C6-sufficient 3xTg-AD mice confirmed a highly significant difference in spine density (Fig. 4d).