阿尔茨海默病中的白质功能障碍与疾病相关的转录组特征有关。

White matter dysfunction in Alzheimer's disease is associated with disease-related transcriptomic signatures.

作者信息

Li Yilu, Zhou Guanyu, Peng Jinzhong, Liu Lin, Zhang Fanyu, Iturria-Medina Yasser, Yao Dezhong, Biswal Bharat B, Wang Pan

机构信息

MOE Key Laboratory for Neuroinformation, The Clinical Hospital of Chengdu Brain Science Institute, Center for Information in Medicine, School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu, China.

Department of Neurology and Neurosurgery, McGill University, Montreal, QC, Canada.

出版信息

Commun Biol. 2025 May 28;8(1):820. doi: 10.1038/s42003-025-08177-7.

DOI:10.1038/s42003-025-08177-7

PMID:40437109

Abstract

While anatomical white matter (WM) alterations in Alzheimer's disease (AD) are well-established, functional WM dysregulation remains rarely investigated. The current study examines WM functional connectivity and network properties alterations in AD and mild cognitive impairment (MCI) and further describes their spatially correlated genes. AD and MCI shared decreased functional connectivity, clustering coefficient, and local efficiency within WM regions involved in impaired sensory-motor, visual-spatial, language, or memory functions. AD-specific dysfunction (i.e., AD vs. MCI and cognitively unimpaired participants) was predominantly located in WM, including anterior and posterior limb of internal capsule, corona radiata, and left tapetum. This WM dysfunction spatially correlates with specific genes, which are enriched in multiple biological processes related to synaptic function and development, and are mostly active in neurons and astrocytes. These findings may contribute to understanding molecular, cellular, and functional signatures associated with WM damage in AD.

摘要

虽然阿尔茨海默病（AD）中解剖学上的白质（WM）改变已得到充分证实，但功能性WM失调仍很少被研究。当前研究考察了AD和轻度认知障碍（MCI）中WM功能连接性和网络属性的改变，并进一步描述了它们在空间上相关的基因。AD和MCI在涉及感觉运动、视觉空间、语言或记忆功能受损的WM区域内，共享功能连接性、聚类系数和局部效率的降低。AD特异性功能障碍（即AD与MCI及认知未受损参与者相比）主要位于WM，包括内囊前肢和后肢、放射冠和左侧毯状层。这种WM功能障碍在空间上与特定基因相关，这些基因在与突触功能和发育相关的多个生物学过程中富集，并且大多在神经元和星形胶质细胞中活跃。这些发现可能有助于理解与AD中WM损伤相关的分子、细胞和功能特征。