Frontotemporal Disorders Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
Brain. 2023 Jan 5;146(1):295-306. doi: 10.1093/brain/awac245.
Posterior cortical atrophy (PCA), usually an atypical clinical syndrome of Alzheimer's disease, has well-characterized patterns of cortical atrophy and tau deposition that are distinct from typical amnestic presentations of Alzheimer's disease. However, the mechanisms underlying the cortical spread of tau in PCA remain unclear. Here, in a sample of 17 biomarker-confirmed (A+/T+/N+) individuals with PCA, we sought to identify functional networks with heightened vulnerability to tau pathology by examining the cortical distribution of elevated tau as measured by 18F-flortaucipir (FTP) PET. We then assessed the relationship between network-specific FTP uptake and visuospatial cognitive task performance. As predicted, we found consistent and prominent localization of tau pathology in the dorsal attention network and visual network of the cerebral cortex. Elevated FTP uptake within the dorsal attention network (particularly the ratio of FTP uptake between the anterior and posterior nodes) was associated with poorer visuospatial attention in PCA; associations were also identified in other functional networks, although to a weaker degree. Furthermore, using functional MRI data collected from each patient at wakeful rest, we found that a greater anterior-to-posterior ratio in FTP uptake was associated with stronger intrinsic functional connectivity between anterior and posterior nodes of the dorsal attention network. Taken together, we conclude that our cross-sectional marker of anterior-to-posterior FTP ratio could indicate tau propagation from posterior to anterior dorsal attention network nodes, and that this anterior progression occurs in relation to intrinsic functional connectivity within this network critical for visuospatial attention. Our findings help to clarify the spatiotemporal pattern of tau propagation in relation to visuospatial cognitive decline and highlight the key role of the dorsal attention network in the disease progression of PCA.
后部皮质萎缩症（PCA）通常是阿尔茨海默病的一种非典型临床综合征，具有明确的皮质萎缩和tau 沉积模式，与典型的阿尔茨海默病遗忘表现明显不同。然而，PCA 中 tau 的皮质扩散的机制尚不清楚。在这里，在 17 名经生物标志物确认的（A+/T+/N+）PCA 个体的样本中，我们通过检查由 18F-flortaucipir（FTP）PET 测量的升高的 tau 的皮质分布，试图确定具有更高 tau 病理学易感性的功能网络。然后，我们评估了特定网络的 FTP 摄取与视觉空间认知任务表现之间的关系。正如预测的那样，我们在大脑皮质的背侧注意网络和视觉网络中发现了 tau 病理学的一致且明显的定位。背侧注意网络内的 FTP 摄取增加（特别是前后节点之间的 FTP 摄取比）与 PCA 中的视觉空间注意力较差相关；在其他功能网络中也发现了关联，尽管程度较弱。此外，使用从每个患者在清醒休息时收集的功能磁共振成像数据，我们发现，在 FTP 摄取中，前到后的比率越大，背侧注意网络的前到后的节点之间的内在功能连接越强。总之，我们得出结论，我们的 FTP 前后比的横断面标志物可以指示从 PCA 的后到前背侧注意网络节点的 tau 传播，并且这种前向进展与该网络内对视觉空间注意力至关重要的内在功能连接有关。我们的研究结果有助于阐明与视觉空间认知能力下降相关的 tau 传播的时空模式，并突出背侧注意网络在 PCA 疾病进展中的关键作用。
