Department of Neurology, Harvard Medical School, MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital, Charlestown, MA,United States.
Department of Radiology, Massachusetts General Hospital, Athinoula A. Martinos Center for Biomedical Imaging, Charlestown, MA,United States.
Curr Alzheimer Res. 2021;18(9):711-720. doi: 10.2174/1567205018666211126113904.
Reduced cerebrovascular function and accumulation of tau pathology are key components of cognitive decline in Alzheimer's disease (AD). Recent multimodal neuroimaging studies show a correlation between cortical tau accumulation and reduced cerebral perfusion. However, animal models predict that tau exerts capillary-level changes that may not be fully captured by standard imaging protocols.
Using newly-developed magnetic resonance imaging (MRI) technology to measure capillary- specific perfusion parameters, we examined a series of mild cognitive impairment (MCI) and AD patients with tau positron emission tomography (PET) to observe whole-brain capillary perfusion alterations and their association with tau deposition.
Seven subjects with MCI or AD received Flortaucipir PET to measure tau deposition and spin-echo dynamic susceptibility contrast (SE-DSC) MRI to measure microvascular perfusion (<10μm radius vessels). Gradient-echo (GE) DSC and pseudocontinuous arterial spin labeling (PCASL) MRI were also acquired to assess macrovascular perfusion. Tau PET, microvascular perfusion, and cortical thickness maps were visually inspected in volumetric slices and on cortical surface projections.
High tau PET signal was generally observed in the lateral temporal and parietal cortices, with uptake in the occipital cortex in one subject. Global blood flow measured by PCASL was reduced with increasing tau burden, which was consistent with previous studies. Tau accumulation was spatially associated with variable patterns of microvascular cerebral blood flow (CBF) and oxygen extraction fraction (OEF) in the cortex and with increased capillary transit heterogeneity (CTH) in adjacent periventricular white matter, independent of amyloid-β status.
Although macrovascular perfusion generally correlated with tau deposition at the whole-cortex level, regional changes in microvascular perfusion were not uniformly associated with either tau pathology or cortical atrophy. This work highlights the heterogeneity of AD-related brain changes and the challenges of implementing therapeutic interventions to improve cerebrovascular function.
脑血管功能下降和 tau 病理学的积累是阿尔茨海默病（AD）认知能力下降的关键组成部分。最近的多模态神经影像学研究表明，皮质 tau 积累与脑灌注减少之间存在相关性。然而，动物模型预测 tau 会引起毛细血管水平的变化，而这些变化可能无法通过标准成像方案完全捕捉到。
使用新开发的磁共振成像（MRI）技术测量毛细血管特异性灌注参数，我们检查了一系列轻度认知障碍（MCI）和 AD 患者的 tau 正电子发射断层扫描（PET），以观察全脑毛细血管灌注变化及其与 tau 沉积的关系。
7 名 MCI 或 AD 患者接受 Flortaucipir PET 测量 tau 沉积和自旋回波动态对比磁共振成像（SE-DSC）测量微血管灌注（<10μm 半径血管）。还采集梯度回波（GE）DSC 和伪连续动脉自旋标记（PCASL）MRI 以评估大血管灌注。在容积切片和皮质表面投影上对 tau PET、微血管灌注和皮质厚度图进行视觉检查。
高 tau PET 信号通常在外侧颞叶和顶叶皮质中观察到，1 名患者在枕叶皮质中有摄取。通过 PCASL 测量的全脑血流量随着 tau 负担的增加而减少，这与之前的研究一致。tau 积累与皮质中微血管脑血流（CBF）和氧提取分数（OEF）的可变模式以及邻近脑室周围白质中毛细血管渡越异质性（CTH）相关，而与淀粉样蛋白-β状态无关。
尽管宏观血流灌注通常与全皮质水平的 tau 沉积相关，但微血管灌注的区域性变化与 tau 病理学或皮质萎缩并不完全相关。这项工作强调了 AD 相关脑变化的异质性和实施改善脑血管功能的治疗干预的挑战。
