Tau PET has allowed for critical insights into in vivo patterns of tau accumulation and change in individuals early in the Alzheimer's disease (AD) continuum. A key methodological step in tau PET analyses is the selection of a reference region, but there is not yet consensus on the optimal region especially for longitudinal tau PET analyses. This study examines how reference region selection influences results related to disease stage at baseline and over time. Longitudinal flortaucipir ([18F]-AV1451) PET scans were examined using several common reference regions (e.g., eroded subcortical white matter, inferior cerebellar gray matter) in 62 clinically unimpaired amyloid negative (CU A-) individuals, 73 CU amyloid positive (CU A+) individuals, and 64 amyloid positive individuals with mild cognitive impairment (MCI A+) from the Alzheimer's Disease Neuroimaging Initiative (ADNI). Cross-sectionally, both reference regions resulted in robust group differences between CU A-, CU A+, and MCI A+ groups, along with significant associations with CSF phosphorylated tau (pTau-181). However, these results were more focally specific and akin to Braak Staging when using eroded white matter, whereas effects with inferior cerebellum were globally distributed across most cortical regions. Longitudinally, utilization of eroded white matter revealed significant accumulation greater than zero across more regions whereas change over time was diminished using inferior cerebellum. Interestingly, the inferior temporal target region seemed most robust to reference region selection with expected cross-sectional and longitudinal signal across both reference regions. With few exceptions, baseline tau did not significantly predict longitudinal change in tau in the same region regardless of reference region. In summary, reference region selection deserves further evaluation as this methodological step may lead to disparate findings. Inferior cerebellar gray matter may be more sensitive to cross-sectional flortaucipir differences, whereas eroded subcortical white matter may be more sensitive for longitudinal analyses examining regional patterns of change.

Tau PET 允许对阿尔茨海默病 (AD) 连续体早期个体的 tau 积累和变化的体内模式进行批判性洞察。tau PET 分析的一个关键方法步骤是参考区域的选择，但对于最佳区域尚未达成共识，尤其是纵向 tau PET 分析。本研究检查了参考区域选择如何影响基线和随时间推移与疾病阶段相关的结果。在 62 名临床上未受损的淀粉样蛋白阴性 ( CU A- ) 个体、73 CU 淀粉样蛋白阳性 (铜A+) 个体，以及来自阿尔茨海默氏病神经影像学倡议 (ADNI) 的64 名具有轻度认知障碍 (MCI A +) 的淀粉样蛋白阳性个体。从横截面上看，两个参考区域都导致 CU A-、CU A + 和 MCI A之间存在显着的组差异+ 组，以及与 CSF 磷酸化 tau (pTau-181) 的显着关联。然而，这些结果在使用侵蚀的白质时更具局灶性，类似于 Braak 分期，而小脑下部的影响在全球分布在大多数皮质区域。从纵向上看，利用被侵蚀的白质显示在更多区域的显着积累大于零，而使用小脑下部则随着时间的推移而减少。有趣的是，下颞靶区似乎对参考区选择最稳健，两个参考区都有预期的横截面和纵向信号。除了少数例外，无论参考区域如何，基线 tau 都不能显着预测同一区域 tau 的纵向变化。总之，参考区域的选择值得进一步评估，因为这一方法步骤可能会导致不同的结果。小脑下部灰质可能对横截面的 flortaucipir 差异更敏感，而被侵蚀的皮层下白质可能对检查区域变化模式的纵向分析更敏感。