Zhao Zhiyong, Cao Zuozhen, Zhu Qinfeng, Xu Haoan, Li Sihui, Zhu Liangying, Xu Guojun, Zhu Keqing, Zhang Jing, Wu Dan
Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, China.
Key Laboratory for Biomedical Engineering of Ministry of Education, Department of Biomedical Engineering, College of Biomedical Engineering & Instrument Science, Zhejiang University, Hangzhou, China.
Hum Brain Mapp. 2025 May;46(7):e70222. doi: 10.1002/hbm.70222.
The laminar-specific distributions of Aβ and Tau deposition in the neocortex of Alzheimer's disease (AD) have been established. However, direct evidence about the effect of AD pathology on cortical microstructure is lacking in human studies. We performed high-resolution T2-weighted and diffusion-weighted MRI (dMRI) on 15 ex vivo whole-hemisphere specimens, including eight cases with low AD neuropathologic change, three cases with primary age-related tauopathy (PART), and four healthy controls (HCs). Using the diffusion tensor model, we evaluated microstructure patterns in six layers of gray matter cortex and performed MRI-histology correlation analysis across cortical layers. Aβ-positive cases exhibited higher diffusivity than Aβ-negative cases (PART and HC) in selected cortical regions, particularly in the inferior frontal cortex. Both Aβ/Tau depositions and dMRI-based microstructural markers demonstrated distinct cortical layer-dependent and region-specific patterns. A significant positive correlation was observed between increased diffusivity and Aβ burden across six cortical layers but not with Tau burden. Furthermore, the mean diffusivity in layer V of the inferior frontal cortex significantly increased with the Amyloid stage. Our findings demonstrate a layer-dependent effect of Aβ pathology on cortical microstructure of the human brain, which may be used to serve as a marker of low AD neuropathologic change.
阿尔茨海默病（AD）新皮质中β-淀粉样蛋白（Aβ）和 Tau 蛋白沉积的层特异性分布已经明确。然而，在人体研究中，缺乏关于 AD 病理对皮质微观结构影响的直接证据。我们对 15 个离体全脑半球标本进行了高分辨率 T2 加权和扩散加权磁共振成像（dMRI），其中包括 8 例 AD 神经病理改变程度较低的病例、3 例原发性年龄相关性 Tau 蛋白病（PART）病例和 4 例健康对照（HC）。我们使用扩散张量模型评估了灰质皮质六层中的微观结构模式，并对皮质各层进行了 MRI 与组织学的相关性分析。在选定的皮质区域，尤其是额下回，Aβ 阳性病例的扩散率高于 Aβ 阴性病例（PART 和 HC）。Aβ/Tau 蛋白沉积和基于 dMRI 的微观结构标记物均表现出明显的皮质层依赖性和区域特异性模式。在六个皮质层中，扩散率增加与 Aβ 负荷之间存在显著正相关，但与 Tau 蛋白负荷无关。此外，额下回 V 层的平均扩散率随淀粉样蛋白阶段显著增加。我们的研究结果表明，Aβ 病理对人脑皮质微观结构具有层依赖性影响，这可能用作 AD 神经病理改变程度较低的一个标志物。
