Objective. In recent studies, network control theory has been applied to clarify transitions between brain states, emphasizing the significance of assessing the controllability of brain networks in facilitating transitions from one state to another. Despite these advancements, the potential alterations in functional network controllability associated with Alzheimer’s disease (AD), along with the underlying genetic mechanisms responsible for these alterations, remain unclear. Approach. We conducted a comparative analysis of functional network controllability measures between patients with AD (n = 64) and matched normal controls (NCs, n = 64). We investigated the association between altered controllability measures and cognitive function in AD. Additionally, we conducted correlation analyses in conjunction with the Allen Human Brain Atlas to identify genes whose expression was correlated with changes in functional network controllability in AD, followed by a set of analyses on the functional features of the identified genes. Main results. In comparison to NCs, patients with AD exhibited a reduction in average controllability, predominantly within the default mode network (DMN) (63% of parcellations), and an increase in average controllability within the limbic (LIM) network (33% of parcellations). Conversely, AD patients displayed a decrease in modal controllability within the LIM network (27% of parcellations) and an increase in modal controllability within the DMN (80% of parcellations). In AD patients, a significant positive correlation was found between the average controllability of the salience network and the mini-mental state examination scores. The changes in controllability measures exhibited spatial correlation with transcriptome profiles. The significant genes identified exhibited enrichment in neurobiologically relevant pathways and demonstrated preferential expression in various tissues, cell types, and developmental periods. Significance. Our findings have the potential to offer new insights into the genetic mechanisms underlying alterations in the controllability of functional networks in AD. Additionally, these results offered perspectives for a deeper understanding of the pathogenesis and the development of therapeutic strategies for AD.

中文翻译：

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阿尔茨海默病的功能性脑网络可控性功能障碍及其与认知和基因表达谱的关系

客观的。在最近的研究中，网络控制理论已被应用于阐明大脑状态之间的转换，强调评估大脑网络的可控性对于促进从一种状态到另一种状态的转换的重要性。尽管取得了这些进展，但与阿尔茨海默病（AD）相关的功能网络可控性的潜在改变，以及导致这些改变的潜在遗传机制仍不清楚。方法。我们对 AD 患者之间的功能网络可控性测量进行了比较分析（n= 64）和匹配的正常对照（NC，n= 64）。我们研究了 AD 中可控性测量改变与认知功能之间的关联。此外，我们结合艾伦人脑图谱进行了相关性分析，以确定其表达与 AD 功能网络可控性变化相关的基因，然后对所识别基因的功能特征进行了一系列分析。主要结果。与 NC 相比，AD 患者表现出平均可控性降低，主要是在默认模式网络 (DMN)（占分区的 63%）内，而边缘系统 (LIM) 网络内的平均可控性增加（占分区的 33%） 。相反，AD 患者在 LIM 网络内表现出模态可控性下降（27% 的分区），而在 DMN 内表现出模态可控性增加（80% 的分区）。在 AD 患者中，显着网络的平均可控性与简易精神状态检查分数之间发现显着的正相关。可控性测量的变化表现出与转录组谱的空间相关性。鉴定出的重要基因在神经生物学相关途径中表现出丰富性，并在各种组织、细胞类型和发育时期表现出优先表达。意义。我们的研究结果有可能为 AD 功能网络可控性改变的遗传机制提供新的见解。此外，这些结果为更深入地了解 AD 的发病机制和制定治疗策略提供了视角。