Department of Radiology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China; Institute for Stroke and Dementia Research (ISD), University Hospital, Ludwig Maximilian University (LMU), Munich, Germany.
Institute for Stroke and Dementia Research (ISD), University Hospital, Ludwig Maximilian University (LMU), Munich, Germany.
Neuroimage Clin. 2024;44:103699. doi: 10.1016/j.nicl.2024.103699. Epub 2024 Oct 30.
Fibrillar tau gradually progresses in the brain during the course of Alzheimer's disease (AD). However, the contribution of tau accumulation in a given brain region to decline in different cognitive domains and thus phenotypic heterogeneity in AD remains unclear. Here, we leveraged the functional connectome to link the locality of tau accumulation to domain-specific cognitive impairment. In the current study, we mapped regional tau-PET accumulation onto the normative functional connectome. Subsequently, we cross-validated in two samples of AD-patients the associations between the tau-connectivity profiles and cognitive domains (episodic memory, executive function, or language). Lastly, we tested the effect of local tau-PET accumulation on the domain-specific tau-lesion networks and cognition. We identified cognitive-domain-specific tau-lesion networks, where closer topological proximity of tau-PET locations to a network was predictive of worse impairment in that domain. Higher tau-PET was associated with decreased domain-specific network connectivity, and the decrease in connectivity was associated with lower domain-specific cognition. The tau locations' connectivity profile explained domain-specific cognitive impairment, where disrupted connectivity may underlie the effect of tau on cognitive impairment.
在阿尔茨海默病（AD）的病程中，纤维状的 tau 蛋白逐渐在大脑中积累。然而，在特定脑区 tau 积累对不同认知领域下降的贡献，以及 AD 表型异质性仍不清楚。在这里，我们利用功能连接组学将 tau 积累的局部性与特定认知领域的损害联系起来。在当前的研究中，我们将区域性 tau-PET 积累映射到规范的功能连接组上。随后，我们在两个 AD 患者样本中进行了交叉验证，以检验 tau 连接模式与认知领域（情景记忆、执行功能或语言）之间的关联。最后，我们测试了局部 tau-PET 积累对特定领域 tau 病变网络和认知的影响。我们确定了认知领域特异性的 tau 病变网络，其中 tau-PET 位置与网络的拓扑接近程度与该领域的损伤程度更差相关。tau-PET 水平越高，与特定领域的网络连接性越低，而连接性的降低与特定领域的认知能力越低相关。tau 位置的连接组模式解释了特定领域的认知障碍，其中连接的破坏可能是 tau 对认知障碍影响的基础。
