Bourgeat P, Krishnadas N, Doré V, Mulligan R, Tyrrell R, Bozinovski S, Huang K, Fripp J, Villemagne V L, Rowe C C
Pierrick Bourgeat, The Australian e-Health Research Centre, CSIRO, Level 7, 296 Herston Road, Herston Qld 4029, Australia, Tel: 07 3253 3659,
J Prev Alzheimers Dis. 2023;10(2):251-258. doi: 10.14283/jpad.2023.17.
Longitudinal tau quantification may provide a useful marker of drug efficacy in clinical trials. Different tau PET tracers may have different sensitivity to longitudinal changes, but without a head-to-head dataset or a carefully designed case-matching procedure, comparing results in different cohorts can be biased. In this study, we compared the tau PET tracers, 18F-MK6240 and 18F-flortaucipir (FTP), both cross-sectionally and longitudinally by case-matching subjects in the AIBL and ADNI longitudinal cohort studies.
A subset of 113 participants from AIBL and 113 from ADNI imaged using 18F-MK6240 and 18F-FTP respectively, with baseline and follow-up, were matched based on baseline clinical diagnosis, MMSE, age and amyloid (Aβ) PET centiloid value. Subjects were grouped as 64 Aβ- cognitively unimpaired (CU), 22 Aβ+ CU, 14 Aβ+ mild cognitive impairment (MCI) and 13 Aβ+ Alzheimer's disease (AD). Tracer retention was measured in the mesial, temporoparietal, rest of the cortex, and a meta-temporal region composed of entorhinal, inferior/middle temporal, fusiform, parahippocampus and amygdala. T-tests were employed to assess group separation at baseline using SUVR Z-scores and longitudinally using SUVR%/Yr.
Both tracers detected statistically significant differences at baseline in most regions between all clinical groups. Only 18F-MK6240 showed statistically significant higher rate of SUVR increase in Aβ+ CU compared to Aβ- CU in the mesial, meta-temporal and temporoparietal regions.
18F-MK6240 appears to be a more sensitive tracer for change in tau level at the preclinical stage of AD.
纵向tau定量分析可能为临床试验中的药物疗效提供有用的标志物。不同的tau PET示踪剂对纵向变化可能具有不同的敏感性,但如果没有直接对比的数据集或精心设计的病例匹配程序,比较不同队列的结果可能会产生偏差。在本研究中,我们通过在AIBL和ADNI纵向队列研究中对受试者进行病例匹配,从横断面和纵向两个方面比较了tau PET示踪剂18F-MK6240和18F-氟代tau蛋白显像剂(FTP)。
分别使用18F-MK6240和18F-FTP对AIBL的113名参与者和ADNI的113名参与者进行成像,这些参与者均有基线和随访数据,并根据基线临床诊断、简易精神状态检查表(MMSE)、年龄和淀粉样蛋白(Aβ)PET百分位数进行匹配。受试者分为64名Aβ-认知未受损(CU)、22名Aβ+ CU、14名Aβ+轻度认知障碍(MCI)和13名Aβ+阿尔茨海默病(AD)。在海马内侧、颞顶叶、皮质其他区域以及由内嗅皮质、颞叶下/中回、梭状回、海马旁回和杏仁核组成的颞叶综合区域测量示踪剂滞留情况。采用t检验,使用标准化摄取值比率(SUVR)Z分数在基线时评估组间差异,使用SUVR%/年在纵向评估组间差异。
两种示踪剂在基线时均在所有临床组的大多数区域检测到具有统计学意义的差异。仅18F-MK6240显示,在海马内侧、颞叶综合区域和颞顶叶区域,与Aβ-CU相比,Aβ+ CU的SUVR增加率具有统计学意义的更高。
18F-MK6240似乎是AD临床前期tau水平变化更敏感的示踪剂。