Figure 7
Validation of the time course of neuronal loss in the caudate nucleus using Model A-C. (A, F, H) When the risk of neuronal damage with a repeat number of 39 was defined as 1, the relative risks of neuronal damage were obtained from the correlation of polyQ size versus post-mortem striatal cell loss divided by subject age (pink circles) or by the correlation of polyQ size versus 1/reciprocal age at onset (blue circles) [42]. Using the time courses of neuronal loss estimated from each model, the relative risks of neuronal damage per polyQ-length were calculated by the age at 65% neuronal loss (red circles) and 30% neuronal loss (black circles) in a similar manner. (B-E, G, I) The predicted LOWESS plots of QNE scores versus disease duration for 41, 47 and 53 repeats were used [17]. The data on the estimated time courses of neuronal loss in each model were transformed to show the relationship between percentage of neuronal loss and disease duration from age at onset for patients with 41, 47 or 53 repeats. Here, the QNE scores and the percentage neuronal losses in the caudate nucleus against disease duration for 41 repeats or 47 repeats were divided by those for 53 repeats. Because QNE score is lineally increased by longer polyQ repeats during disease progression [17], we investigated the linear correlation between [(QNE scores at 41 repeats/QNE scores at 53 repeats) ÷ (neuronal losses at 41 repeats/neuronal losses at 53 repeats)] and [(QNE scores at 47 repeats/QNE scores at 53 repeats) ÷ (neuronal losses at 47 repeats/neuronal losses at 53 repeats)] (QNE[41/53]/NL[41/53] versus QNE[47/53]/NL[47/53]). We calculated the time courses of neuronal loss when neurons number account 30% of baseline at disease onset (B, G, I). In Model A, we also calculated when neurons number account 20 (C), 40 (D) or 50% (E) of baseline at disease onset.