Our understanding on human neurodegenerative disease was previously limited to clinical data and inferences about the underlying pathology based on histopathological examination. Animal models and in vitro experiments have provided evidence for a cell-autonomous and a non-cell-autonomous mechanism for the accumulation of neuropathology. Combining modern neuroimaging tools to identify distinct neural networks (connectomics) with target-specific positron emission tomography (PET) tracers is an emerging and vibrant field of research with the potential to examine the contributions of cell-autonomous and non-cell-autonomous mechanisms to the spread of pathology. The evidence provided here suggests that both cell-autonomous and non-cell-autonomous processes relate to the observed in vivo characteristics of protein pathology and neurodegeneration across the disease spectrum. We propose a synergistic model of cell-autonomous and non-cell-autonomous accounts that integrates the most critical factors (i.e., protein strain, susceptible cell feature and connectome) contributing to the development of neuronal dysfunction and in turn produces the observed clinical phenotypes. We believe that a timely and longitudinal pursuit of such research programs will greatly advance our understanding of the complex mechanisms driving human neurodegenerative diseases.

中文翻译：

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神经变性中的连接组学和分子成像。

我们对人类神经退行性疾病的理解以前仅限于临床数据和基于组织病理学检查的潜在病理学推断。动物模型和体外实验为神经病理学积累的细胞自主和非细胞自主机制提供了证据。将现代神经成像工具与目标特异性正电子发射断层扫描 (PET) 示踪剂相结合以识别不同的神经网络（连接组学）是一个新兴且充满活力的研究领域，有可能检查细胞自主和非细胞自主机制的贡献病理学的传播。这里提供的证据表明，细胞自主和非细胞自主过程都与在整个疾病谱中观察到的蛋白质病理学和神经变性的体内特征有关。我们提出了一个细胞自主和非细胞自主账户的协同模型，该模型整合了导致神经元功能障碍发展的最关键因素（即蛋白质菌株、易感细胞特征和连接组），进而产生观察到的临床表型。我们相信，及时和纵向地开展此类研究计划将极大地促进我们对驱动人类神经退行性疾病的复杂机制的理解。蛋白菌株、易感细胞特征和连接组）有助于神经元功能障碍的发展，进而产生观察到的临床表型。我们相信，及时和纵向地开展此类研究计划将极大地促进我们对驱动人类神经退行性疾病的复杂机制的理解。蛋白菌株、易感细胞特征和连接组）有助于神经元功能障碍的发展，进而产生观察到的临床表型。我们相信，及时和纵向地开展此类研究计划将极大地促进我们对驱动人类神经退行性疾病的复杂机制的理解。