PMC3034479_01
Representative FDDNP-PET (left), T1-weighted MRI (middle) and FDG-PET (right) images in the index patient. Note the left lateral parietotemporal area with relatively decreased metabolism on FDG, and the more inferior lateral temporal area with increased FDDNP signal. Also seen is increased FDDNP signal in the caudate head and anterior putamina bilaterally.
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F1
FDG-PET revealed diffuse left cortical hypometabolism, particularly evident in the parietal cortex (Figure 1), where FDG metabolism fell 2.6 SD's below the mean of normal controls. FDDNP binding was also substantially elevated in the heads of the caudate nuclei and anterior putamina bilaterally (Figure 1) with DVRs 5 SD's higher than in controls and 1.5 SDs above that in AD patients with a mean age of 72 years.
Striatal Abeta (A, 20X) and tau pathology (B, 40X and D, 400X) in the case with an S212Y PSEN1 mutation. In comparison to a sporadic Alzheimer's disease (AD) case (C, 400X, Braak stage VI), the tau pathology was substantially more severe. No difference was observed in the severity of Abeta deposition between the familial AD case and sporadic AD cases.
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F2
Striatal tau pathology was severe in comparison to sporadic Braak VI Alzheimer's disease (Figure 2).
PMC3034479_02
Average production of Abeta42 in a cellular model in which wild type PS1 (PS1 WT), the S212Y substitution, I238M substitution (another potential novel mutation), the delta 9 deletion, and control (GFP) constructs have been introduced. *p <= 0.001
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F3
Levels of Abeta42 produced by cells in which the S212Y mutation was introduced were 2.4x those produced by cells with WT PS1 (p = 4.5 x 10-8, Figure 3).