Aghakhanyan Gayane, Rullmann M, Rumpf J, Schroeter M L, Scherlach C, Patt M, Brendel M, Koglin N, Stephens A W, Classen J, Hoffmann K T, Sabri O, Barthel H
Department of Nuclear Medicine, University of Leipzig, Leipzig, Germany.
Department of Translational Research and of New Surgical and Medical Technologies, University of Pisa, Pisa, Italy.
Eur J Nucl Med Mol Imaging. 2022 Dec;50(1):103-114. doi: 10.1007/s00259-022-05952-0. Epub 2022 Sep 1.
Progressive supranuclear palsy (PSP) is primary 4-repeat tauopathy. Evidence spanning from imaging studies indicate aberrant connectivity in PSPs. Our goal was to assess functional connectivity network alterations in PSP patients and the potential link between regional tau-burden and network-level functional connectivity using the next-generation tau PET tracer [F]PI-2620 and resting-state functional MRI (fMRI).
Twenty-four probable PSP patients (70.9 ± 6.9 years, 13 female), including 14 Richardson syndrome (RS) and 10 non-RS phenotypes, underwent [F]PI-2620 PET/MRI imaging. Distribution volume ratios (DVRs) were estimated using non-invasive pharmacokinetic modeling. Resting-state fMRI was also acquired in these patients as well as in thirteen older non-AD MCI reference group (64 ± 9 years, 4 female). The functional network was constructed using 141 by 141 region-to-region functional connectivity metrics (RRC) and network-based statistic was carried out (connection threshold p < 0.001, cluster threshold pFDR < 0.05).
In total, 9870 functional connections were analyzed. PSPs compared to aged non-AD MCI reference group expressed aberrant connectivity evidenced by the significant NBS network consisting of 89 ROIs and 118 connections among them (NBS mass 4226, pFDR < 0.05). Tau load in the right globus pallidus externus (GPe) and left dentate nucleus (DN) showed significant effects on functional network connectivity. The network linked with increased tau load in the right GPe was associated with hyperconnectivity of low-range intra-opercular connections (NBS mass 356, pFDR < 0.05), while the network linked with increased tau load in the left cerebellar DN was associated with cerebellar hyperconnectivity and cortico-cerebellar hypoconnectivity (NBS mass 517, pFDR < 0.05).
PSP patients show altered functional connectivity. Network incorporating deep gray matter structures demonstrate hypoconnectivity, cerebellum hyperconnectivity, while cortico-cortical connections show variable changes. Tau load in the right GPe and left DN is associated with functional networks which strengthen low-scale intra-opercular and intra-cerebellar connections and weaken opercular-cerebellar connections. These findings support the concept of tau load-dependent functional network changes in PSP, by that providing evidence for downstream effects of neuropathology on brain functionality in this primary tauopathy.
进行性核上性麻痹（PSP）是原发性4重复tau蛋白病。影像学研究的证据表明PSP患者存在异常连接。我们的目标是使用新一代tau正电子发射断层显像（PET）示踪剂[F]PI - 2620和静息态功能磁共振成像（fMRI），评估PSP患者的功能连接网络改变以及区域tau负荷与网络水平功能连接之间的潜在联系。
24例很可能患有PSP的患者（70.9±6.9岁，13名女性），包括14例理查森综合征（RS）和10例非RS表型，接受了[F]PI - 2620 PET/MRI成像。使用非侵入性药代动力学模型估计分布容积比（DVR）。这些患者以及13名年龄较大的非阿尔茨海默病轻度认知障碍（MCI）参考组患者（64±9岁，4名女性）也进行了静息态fMRI检查。使用141×141的区域间功能连接度量（RRC）构建功能网络，并进行基于网络的统计分析（连接阈值p < 0.001，聚类阈值pFDR < 0.05）。
总共分析了9870个功能连接。与年龄较大的非AD MCI参考组相比，PSP患者表现出异常连接，由一个由89个感兴趣区（ROI）和它们之间118个连接组成的显著基于网络的统计（NBS）网络证明（NBS质量4226，pFDR < 0.05）。右侧苍白球外侧部（GPe）和左侧齿状核（DN）中的tau负荷对功能网络连接有显著影响。与右侧GPe中tau负荷增加相关的网络与低范围的眶内连接的高连接性有关（NBS质量356，pFDR < 0.05），而与左侧小脑DN中tau负荷增加相关的网络与小脑高连接性和皮质 - 小脑低连接性有关（NBS质量517，pFDR < 0.05）。
PSP患者表现出功能连接改变。包含深部灰质结构的网络显示低连接性，小脑高连接性，而皮质 - 皮质连接显示出可变变化。右侧GPe和左侧DN中的tau负荷与功能网络相关，这些网络增强了低尺度的眶内和小脑内连接，并削弱了眶 - 小脑连接。这些发现支持了PSP中tau负荷依赖性功能网络变化的概念，从而为这种原发性tau蛋白病中神经病理学对脑功能的下游影响提供了证据。
