BACKGROUND The human brain is complex and interconnected structurally. Brain connectome change is associated with Alzheimer's disease (AD) and other neurodegenerative diseases. Genetics and genomics studies have identified molecular changes in AD; however, the results are often limited to isolated brain regions and are difficult to interpret its findings in respect to brain connectome. The mechanisms of how one brain region impacts the molecular pathways in other regions have not been systematically studied. And how the brain regions susceptible to AD pathology interact with each other at the transcriptome level and how these interactions relate to brain connectome change are unclear. METHODS Here, we compared structural brain connectomes defined by probabilistic tracts using diffusion magnetic resonance imaging data in Alzheimer's Disease Neuroimaging Initiative database and a brain transcriptome dataset covering 17 brain regions. RESULTS We observed that the changes in diffusion measures associated with AD diagnosis status and the associations were replicated in an independent cohort. The result suggests that disease associated white matter changes are focal. Analysis of the brain connectome by genomic data, tissue-tissue transcriptional synchronization between 17 brain regions, indicates that the regions connected by AD-associated tracts were likely connected at the transcriptome level with high number of tissue-to-tissue correlated (TTC) gene pairs (P = 0.03). And genes involved in TTC gene pairs between white matter tract connected brain regions were enriched in signaling pathways (P = 6.08 × 10-9). Further pathway interaction analysis identified ionotropic glutamate receptor pathway and Toll receptor signaling pathways to be important for tissue-tissue synchronization at the transcriptome level. Transcript profile entailing Toll receptor signaling in the blood was significantly associated with diffusion properties of white matter tracts, notable association between fractional anisotropy and bilateral cingulum angular bundles (Ppermutation = 1.0 × 10-2 and 4.9 × 10-4 for left and right respectively). CONCLUSIONS In summary, our study suggests that brain connectomes defined by MRI and transcriptome data overlap with each other.

中文翻译：

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通过 MRI 和基因组学比较大脑连接体及其在阿尔茨海默病中的意义。


背景技术人脑在结构上是复杂且相互关联的。大脑连接组的变化与阿尔茨海默病（AD）和其他神经退行性疾病有关。遗传学和基因组学研究已经确定了 AD 的分子变化；然而，结果通常仅限于孤立的大脑区域，并且很难解释其关于大脑连接组的发现。大脑某一区域如何影响其他区域分子通路的机制尚未得到系统研究。易受 AD 病理影响的大脑区域如何在转录组水平上相互作用以及这些相互作用与大脑连接组变化有何关系尚不清楚。方法在这里，我们使用阿尔茨海默病神经影像计划数据库中的扩散磁共振成像数据和覆盖 17 个大脑区域的大脑转录组数据集比较了由概率束定义的结构性大脑连接组。结果 我们观察到，与 AD 诊断状态相关的扩散测量值的变化以及这种关联在一个独立队列中得到了重复。结果表明，与疾病相关的白质变化是焦点。通过基因组数据对大脑连接组进行分析，即 17 个大脑区域之间的组织-组织转录同步，表明 AD 相关束连接的区域可能在转录组水平上与大量组织间相关 (TTC) 基因相关对（P = 0.03）。白质束连接脑区之间的 TTC 基因对涉及的基因在信号通路中富集（P = 6.08 × 10-9）。 进一步的通路相互作用分析发现离子型谷氨酸受体通路和 Toll 受体信号通路对于转录组水平的组织-组织同步非常重要。血液中 Toll 受体信号传导的转录谱与白质束的扩散特性显着相关，分数各向异性和双侧扣带回角束之间显着相关（Ppermutation = 1.0 × 10-2 和 4.9 × 10-4 分别为左和右） 。结论 总之，我们的研究表明 MRI 和转录组数据定义的大脑连接体相互重叠。