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.
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).
In summary, our study suggests that brain connectomes defined by MRI and transcriptome data overlap with each other.
这里,我们使用阿尔茨海默病神经影像学计划数据库中的弥散磁共振成像数据和覆盖17个脑区的脑转录组数据集,比较了由概率束定义的结构性脑连接组.
我们观察到,与AD诊断状态相关的扩散测量的变化和关联在一个独立的队列中重复。结果表明,疾病相关的白质变化是局灶性的。通过基因组数据分析大脑连接体,17个脑区之间的组织-组织转录同步,表明由AD相关束连接的区域可能在转录组水平上与大量的组织到组织相关(TTC)基因对(P=0.03)连接。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确定了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-组织同步是重要的。导致血液中Toll受体信号传导的转录谱与白质束的扩散特性显着相关,各向异性分数与双侧扣带角束之间的显着关联(左右分别为Ppermutation=1.0×10-2和4.9×10-4)。
总之,我们的研究表明,MRI定义的脑连接体和转录组数据相互重叠.