Department of Nuclear Medicine, LMU University Hospital, LMU Munich, Munich, Germany.
Department of Nuclear Medicine, University Hospital Leipzig, Leipzig, Germany.
Eur J Nucl Med Mol Imaging. 2024 Jun;51(7):1909-1922. doi: 10.1007/s00259-024-06637-6. Epub 2024 Feb 17.
We hypothesized that severe tau burden in brain regions involved in direct or indirect pathways of the basal ganglia correlate with more severe striatal dopamine deficiency in four-repeat (4R) tauopathies. Therefore, we correlated [F]PI-2620 tau-positron-emission-tomography (PET) imaging with [I]-Ioflupane single-photon-emission-computed tomography (SPECT) for dopamine transporter (DaT) availability.
Thirty-eight patients with clinically diagnosed 4R-tauopathies (21 male; 69.0 ± 8.5 years) and 15 patients with clinically diagnosed α-synucleinopathies (8 male; 66.1 ± 10.3 years) who underwent [F]PI-2620 tau-PET and DaT-SPECT imaging with a time gap of 3 ± 5 months were evaluated. Regional Tau-PET signals and DaT availability as well as their principal components were correlated in patients with 4R-tauopathies and α-synucleinopathies. Both biomarkers and the residuals of their association were correlated with clinical severity scores in 4R-tauopathies.
In patients with 4R-tauopathies, [F]PI-2620 binding in basal ganglia and midbrain regions was negatively associated with striatal DaT availability (i.e. globus pallidus internus and putamen (β = - 0.464, p = 0.006, Durbin-Watson statistics = 1.824) in a multiple regression model. Contrarily, [F]PI-2620 binding in the dentate nucleus showed no significant regression factor with DaT availability in the striatum (β = 0.078, p = 0.662, Durbin-Watson statistics = 1.686). Patients with α-synucleinopathies did not indicate any regional associations between [F]PI-2620-binding and DaT availability. Higher DaT-SPECT binding relative to tau burden was associated with better clinical performance (β = - 0.522, p = 0.011, Durbin-Watson statistics = 2.663) in patients with 4R-tauopathies.
Tau burden in brain regions involved in dopaminergic pathways is associated with aggravated dopaminergic dysfunction in patients with clinically diagnosed primary tauopathies. The ability to sustain dopamine transmission despite tau accumulation may preserve motor function.
我们假设，在与基底神经节直接或间接通路相关的脑区中存在严重的 tau 负担，与四重复（4R）tau 病患者的纹状体多巴胺缺乏更严重相关。因此，我们将[F]PI-2620 tau 正电子发射断层扫描（PET）成像与[I]-碘代苯丙胺单光子发射计算机断层扫描（SPECT）用于多巴胺转运体（DaT）可用性进行了关联。
对 38 名经临床诊断的 4R-tau 病患者（21 名男性；69.0±8.5 岁）和 15 名经临床诊断的 α-突触核蛋白病患者（8 名男性；66.1±10.3 岁）进行了[F]PI-2620 tau-PET 和 DaT-SPECT 成像评估，两次检查的时间间隔为 3±5 个月。在 4R-tau 病和 α-突触核蛋白病患者中，对纹状体和中脑区域的 tau-PET 信号和 DaT 可用性及其主成分进行了相关性分析。在 4R-tau 病患者中，tau 病标志物及其相关性的残差与临床严重程度评分相关。
在 4R-tau 病患者中，基底节和中脑区域的[F]PI-2620 结合与纹状体 DaT 可用性呈负相关（即苍白球内和壳核（β= -0.464，p= 0.006，Durbin-Watson 统计量=1.824）在多元回归模型中。相反，齿状核中的[F]PI-2620 结合与纹状体中的 DaT 可用性没有显著的回归因子（β=0.078，p=0.662，Durbin-Watson 统计量=1.686）。α-突触核蛋白病患者没有显示出[F]PI-2620 结合与 DaT 可用性之间的任何区域相关性。在 4R-tau 病患者中，与 tau 负荷相比，较高的 DaT-SPECT 结合与更好的临床表现相关（β= -0.522，p=0.011，Durbin-Watson 统计量=2.663）。
在与多巴胺能通路相关的脑区中，tau 负担与临床诊断为原发性 tau 病患者的多巴胺能功能障碍加重相关。尽管 tau 积累，但维持多巴胺传递的能力可能会保持运动功能。
