NeuroSpin, Paris-Saclay University, CEA, CNRS, 91191 Gif-sur-Yvette, France; Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal.; ICVS/3B's, PT Government Associate Laboratory, Braga, Guimarães, Portugal.
Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal.; ICVS/3B's, PT Government Associate Laboratory, Braga, Guimarães, Portugal.
Neurobiol Dis. 2024 Oct 15;201:106679. doi: 10.1016/j.nbd.2024.106679. Epub 2024 Sep 23.
Alzheimer's disease (AD) is characterized by progressive cognitive decline and neuropathological changes, yet the underlying neurobiological mechanisms remain elusive. Here, we employed a multimodal longitudinal neuroimaging approach, using anatomical and functional sequences on a high field magnetic resonance imaging (MRI) preclinical scanner, to investigate alterations in brain connectivity and white matter microstructure in a transgenic mouse model of AD (J20) when compared to wild-type (WT) littermates. Functional connectivity analysis revealed distinct network disruptions in J20 mice, primarily involving connections between posterior and anterior brain regions; importantly, a significant interaction between group and age highlighted an exacerbation of these connectivity changes with advancing age in J20 mice. In addition, significant reductions in fractional anisotropy (FA) were observed in the corpus callosum of J20 mice compared to WT, indicative of microstructural alterations consistent with white matter pathology. The observed alterations in brain connectivity and microstructure provide valuable insights into the spatiotemporal processes underlying AD-related decline and underscore the utility of multimodal neuroimaging in elucidating the neurobiological substrates of AD pathology in animal models.
阿尔茨海默病（AD）的特征是进行性认知能力下降和神经病理学变化，但潜在的神经生物学机制仍难以捉摸。在这里，我们采用了多模态纵向神经影像学方法，使用高场磁共振成像（MRI）临床前扫描仪的解剖和功能序列，来研究与野生型（WT）同窝仔比较时 AD（J20）转基因小鼠模型的脑连接和白质微观结构的变化。功能连接分析显示 J20 小鼠存在明显的网络破坏，主要涉及大脑后区和前区之间的连接；重要的是，组间和年龄间的显著相互作用强调了随着 J20 小鼠年龄的增长，这些连接变化的加剧。此外，与 WT 相比，J20 小鼠的胼胝体的分数各向异性（FA）显著降低，表明与白质病理学一致的微观结构改变。观察到的脑连接和微观结构的改变为 AD 相关衰退的时空过程提供了有价值的见解，并强调了多模态神经影像学在阐明动物模型中 AD 病理学的神经生物学基础方面的效用。
