Discriminatory ability of next-generation tau PET tracers for Alzheimer's disease.
Discriminatory ability of next-generation tau PET tracers for Alzheimer's disease.
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DOI：
10.1093/brain/awab120
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发表时间：
2021-09-04
期刊：
影响因子：
--
通讯作者：
Sander K
中科院分区：
文献类型：
--
作者：
Yap SY;Frias B;Wren MC;Schöll M;Fox NC;Årstad E;Lashley T;Sander K
用于阿尔茨海默病和其他痴呆症成像的下一代tau PET示踪剂最近已经开发出来。虽然新化合物现在已进入临床研究，但可用于评估其临床应用适用性的信息有限。为了了解放射性示踪剂结合图谱的差异，迫切需要进行面对面的比较。我们使用氚标记的放射性示踪剂的定量磷成像结合tau的特异性免疫组织化学，研究了25例痴呆患者和年龄匹配的对照组的人死后脑组织中tau示踪剂PI2620、RO948、MK6240和JNJ067的结合情况。这四种放射性示踪剂描绘了具有高度特异性的由一对螺旋细丝组成的tau包涵体，无论是在阿尔茨海默病病例中，还是在伴随阿尔茨海默病病理的原发牛磺酸病变病例中。相反，在没有成对螺旋微丝tau的病例中，发现皮质与原发肌病的结合在年龄匹配的对照组的范围内。基底节组织中的异源阻断研究表明，脱靶与单胺氧化酶B的结合已经被克服。阿尔茨海默病组内皮质示踪剂结合的高度变异性遵循每种示踪剂的相同模式，这表明所有化合物都适合于区分阿尔茨海默病和其他痴呆症。为了确定下一代tau PET示踪剂的结合图谱，Yap等人。对人类死后脑组织中的四种新化合物进行了面对面的比较。结果表明，这四种示踪剂同样适合于区分阿尔茨海默病与其他痴呆症和对照组。
A next generation of tau PET tracers for the imaging of Alzheimer’s disease and other dementias has recently been developed. Whilst the new compounds have now entered clinical studies, there is limited information available to assess their suitability for clinical applications. Head-to-head comparisons are urgently needed to understand differences in the radiotracer binding profiles. We characterized the binding of the tau tracers PI2620, RO948, MK6240 and JNJ067 in human post-mortem brain tissue from a cohort of 25 dementia cases and age-matched controls using quantitative phosphorimaging with tritium-labelled radiotracers in conjunction with phospho-tau specific immunohistochemistry. The four radiotracers depicted tau inclusions composed of paired helical filaments with high specificity, both in cases with Alzheimer’s disease and in primary tauopathy cases with concomitant Alzheimer’s disease pathology. In contrast, cortical binding to primary tauopathy in cases without paired helical filament tau was found to be within the range of age-matched controls. Off-target binding to monoamine oxidase B has been overcome, as demonstrated by heterologous blocking studies in basal ganglia tissue. The high variability of cortical tracer binding within the Alzheimer’s disease group followed the same pattern with each tracer, suggesting that all compounds are suited to differentiate Alzheimer’s disease from other dementias. To determine the binding profiles of next-generation tau PET tracers, Yap et al. performed a head-to-head comparison of four new compounds in human post-mortem brain tissue. The results suggest that the four tracers are equally well-suited to discriminating Alzheimer's disease from other dementias and from controls.
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