Division of Nuclear Medicine and Molecular Imaging, Massachusetts General Hospital, Boston, MA, USA.
Department of Radiology, Massachusetts General Hospital, Boston, MA, USA.
J Alzheimers Dis. 2018;62(4):1691-1702. doi: 10.3233/JAD-170840.
On target 18F-Flortaucipir (FTP) binding of Alzheimer's disease tau aggregates and off-target binding of melanocytes have been demonstrated with autoradiography.
We aimed to investigate the hypothesis that if binding in choroid plexus (CP) is due to melanocytes, the signal would be elevated in Black/African American (B/AA) compared to White (W) participants. In addition, we examined whether CP signal affects measurements in adjacent regions, and whether correcting for spill-in effects has an influence on associations between hippocampus (HC) FTP and amyloid or cognition.
FTP race differences in 147 Harvard Aging Brain Study participants (23 B/AA, 124W) were examined in CP, HC, HC covaried for CP, amygdala, inferior temporal gyrus, entorhinal cortex, and fusiform regions. Associations between CP FTP and other regions-of-interest (ROIs) were probed to assess spill-in effects. A statistical regression approach to attenuate CP spill-in was tested by relating adjusted HC SUVR residuals and unadjusted HC SUVR to race, cognition and amyloid. All analyses were covaried for age, sex, education and amyloid deposition, and Bonferroni-corrected for multiple comparisons.
B/AA individuals had elevated CP and HC SUVR (p < 0.007), whereas other ROI SUVR and HC SUVR covaried for CP SUVR did not show race differences (p > 0.05). CP SUVR was associated with HC SUVR (p < 10-14), but with no other ROI SUVR (p > 0.05). When adjusting HC SUVR for CP SUVR, no race differences in residual HC SUVR were detected, and relationships with amyloid and memory became apparent.
Melanocyte FTP binding may account partially for high CP signal. This off-target binding affects mainly HC FTP measurements, which should be interpreted with caution.
已有研究通过放射自显影技术证实,阿尔茨海默病tau 聚集物的目标 18F-Flortaucipir(FTP)结合以及黑色素细胞的非目标结合。
我们旨在验证一个假设,如果脉络丛(CP)中的结合是由于黑色素细胞引起的,那么与白种人(W)参与者相比,信号在黑种人/非裔美国人(B/AA)中会升高。此外,我们还研究了 CP 信号是否会影响相邻区域的测量值,以及校正溢出效应是否会影响海马体(HC)FTP 与淀粉样蛋白或认知之间的关联。
在 147 名哈佛衰老大脑研究参与者(23 名 B/AA,124 名 W)中,研究了 FTP 在 CP、HC、CP 校正的 HC、杏仁核、下颞叶、内嗅皮质和梭状回区域的种族差异。探测 CP FTP 与其他感兴趣区域(ROI)之间的关联,以评估溢出效应。通过将校正后的 HC SUVR 残差和未校正的 HC SUVR 与种族、认知和淀粉样蛋白相关联,测试了一种用于减轻 CP 溢出效应的统计回归方法。所有分析均针对年龄、性别、教育和淀粉样蛋白沉积进行了协变量校正,并通过 Bonferroni 校正进行了多次比较。
B/AA 个体的 CP 和 HC SUVR 升高(p<0.007),而其他 ROI SUVR 和 CP 校正的 HC SUVR 则没有显示出种族差异(p>0.05)。CP SUVR 与 HC SUVR 相关(p<10-14),但与其他 ROI SUVR 无关(p>0.05)。当校正 CP SUVR 后,HC SUVR 的残余值中未检测到种族差异,并且与淀粉样蛋白和记忆之间的关系变得明显。
黑色素细胞 FTP 结合可能部分解释了 CP 信号高的原因。这种非目标结合主要影响 HC FTP 的测量值,因此应谨慎解释。