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The Caudate-Putamen: GFAP Staining and MRI-AK

A similar analysis was conducted for the caudate-putamen region. The observed data for GFAP percentage of area stained and MRI-AK shown in Figure 17.12a indicates an age-dependent shift in histology values for transgenic mice and a relatively small shift in MRI-AK values. The estimated disease- level surrogacy is relatively low at R2D = 0.596 (see Figure 17.12b). Moreover,

FIGURE 17.11

The motor cortex region: Individual and disease-level surrogacy for all MRI parameters and histology stains (percentage of area stained).

TABLE 17.3

The caudate-putamen region: Parameter estimate of AD progression effects for GFAP percentage of area stained with MRI-AK. в: disease effect on GFAP percentage of area stained. a: disease effect on MRI-AK.


/3 (s.e.)

a (s.e.)


0.35 (0.43)

-0.0001 (0.02)


1.05 (0.43)

0.02 (0.02)


3.99 (0.46)

-0.013 (0.024)


8.75 (0.46)

0.0001 (0.024)


16.37 (0.80)

0.09 (0.03)

although a large disease effect on histology is observed over time as shown in Table 17.3, the disease effect on MRI is relatively small, hence the low association between MRI and histology disease effects. Similar patterns can be observed for individual-level surrogacy of MRI-AK as a biomarker for GFAP percentage of area stained as shown in Figures 17.13a and b.

Figure 17.14a shows the surrogacy measures for all MRI parameters and histology stains (percentage of area stained) in the caudate-putamen region. For the 4G8 staining, the highest surrogacy measures at a disease level was found for MRI-AD and MRI-MD (R2D = 0.62 and R2D = 0.61, respectively). The MRI parameters with the highest disease-level surrogacy measures in the caudate-putamen region were MRI-MD, MRI-MK, and MRI-RD for the GFAP staining with R2D = 0.83, R2D = 0.87, and R2D = 0.86, respectively. Note that for the MBP staining, all MRI parameters except for MRI-AD (R2D = 0.35), are good biomarkers at disease level with RD > 0.72. For transgenic mice, individual-level surrogacy was very low for all MRI parameters and histology stains as shown in Figure 17.14b. On the other hand, individual-level surrogacy was found to be relatively high in the wildtype mice for MBP staining using MRI-AK (pW = 0.95), MRI-MK (pW = 0.94), MRI-RD (pW = 0.94), and MRI-RK (pW = 0.71).

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