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. 2006 May;168(5):1598–1607. doi: 10.2353/ajpath.2006.050840

Figure 2 .

Figure 2

Region-specific neuronal loss (left) and accumulation of PHF1-positive neurofibrillary pathology (right) were examined in rTg4510 mice. All regions exhibited neuronal loss compared to control animals (average of controls at all ages ± SD, gray bars), and in all regions except striatum, this loss was age-related, as can be seen by the two-way analysis of variance results presented with each graph (age and condition [control, tau, and tau+dox] as independent variables, Bonferroni-Dunn posthoc tests). CA1 and DG undergo the most severe neuron loss. In CA1, 68% of neurons are lost by 5.5 months of age. At this same age, 25% of remaining neurons are PHF1-positive, growing to 56% PHF1-positive by 8.5 months (when 82% of neurons have died). In the dentate gyrus, neurons are lost early (by 2.5 months, P = 0.004) despite the complete absence of PHF1-positive neurons at this age, indicating that neuronal loss can occur before neurofibrillary lesions. rTg4510 CA2/3 and cortex also suffer significant neuronal loss, which reaches 69% and 52%, respectively, by 8.5 months. Suppression of the tau transgene with dox for 6 weeks prevented further neuron loss in all regions at all ages examined (dotted lines). All regions exhibited age-related PHF1-positive accumulation, which began by 2.5 months in the CA1, CA2/3, and cortex, by 5.5 months in striatum, and by 7 months in DG (the asterisks show posthoc comparison of control versus tau at individual ages). Tau transgene suppression did not remove existing neurofibrillary pathology in any region at any age examined. In fact, comparing the number of PHF1-positive neurons at the age when treatment began to the number after 6 weeks of suppression shows an increase in pathology in several cases (black and white asterisk symbols). In CA2/3, suppression from 4 to 5.5 months resulted in a significant prevention of further accumulation, although existing PHF1-positive neurons were not removed. This exception indicates a temporal and regional variability in the effects of transgene suppression.