Chandio Bramsh Qamar, Villalon-Reina Julio E, Nir Talia M, Thomopoulos Sophia I, Feng Yixue, Benavidez Sebastian, Jahanshad Neda, Harezlak Jaroslaw, Garyfallidis Eleftherios, Thompson Paul M
Imaging Genetics Center, Mark and Mary Stevens Neuroimaging and Informatics Institute, Keck School of Medicine, University of Southern California, Marina del Rey, CA, USA,
Imaging Genetics Center, Mark and Mary Stevens Neuroimaging and Informatics Institute, Keck School of Medicine, University of Southern California, Marina del Rey, CA, USA.
Pac Symp Biocomput. 2025;30:394-411. doi: 10.1142/9789819807024_0029.
Alzheimer's disease (AD) is characterized by cognitive decline and memory loss due to the abnormal accumulation of amyloid-beta (Aβ) plaques and tau tangles in the brain; its onset and progression also depend on genetic factors such as the apolipoprotein E (APOE) genotype. Understanding how these factors affect the brain's neural pathways is important for early diagnostics and interventions. Tractometry is an advanced technique for 3D quantitative assessment of white matter tracts, localizing microstructural abnormalities in diseased populations in vivo. In this work, we applied BUAN (Bundle Analytics) tractometry to 3D diffusion MRI data from 730 participants in ADNI3 (phase 3 of the Alzheimer's Disease Neuroimaging Initiative; age range: 55-95 years, 349M/381F, 214 with mild cognitive impairment, 69 with AD, and 447 cognitively healthy controls). Using along-tract statistical analysis, we assessed the localized impact of amyloid, tau, and APOE genetic variants on the brain's neural pathways. BUAN quantifies microstructural properties of white matter tracts, supporting along-tract statistical analyses that identify factors associated with brain microstructure. We visualize the 3D profile of white matter tract associations with tau and amyloid burden in Alzheimer's disease; strong associations near the cortex may support models of disease propagation along neural pathways. Relative to the neutral genotype, APOE ϵ3/ϵ3, carriers of the AD-risk conferring APOE ϵ4 genotype show microstructural abnormalities, while carriers of the protective ϵ2 genotype also show subtle differences. Of all the microstructural metrics, mean diffusivity (MD) generally shows the strongest associations with AD pathology, followed by axial diffusivity (AxD) and radial diffusivity (RD), while fractional anisotropy (FA) is typically the least sensitive metric. Along-tract microstructural metrics are sensitive to tau and amyloid accumulation, showing the potential of diffusion MRI to track AD pathology and map its impact on neural pathways.
阿尔茨海默病（AD）的特征是由于大脑中β淀粉样蛋白（Aβ）斑块和tau缠结的异常积累导致认知能力下降和记忆丧失；其发病和进展还取决于遗传因素，如载脂蛋白E（APOE）基因型。了解这些因素如何影响大脑的神经通路对于早期诊断和干预至关重要。纤维束成像术是一种用于对白质纤维束进行三维定量评估的先进技术，可在体内定位患病群体中的微观结构异常。在这项研究中，我们将束分析（BUAN）纤维束成像术应用于阿尔茨海默病神经成像计划第三阶段（ADNI3）中730名参与者的三维扩散磁共振成像（MRI）数据（年龄范围：55 - 95岁，349名男性/381名女性，214名轻度认知障碍患者，69名AD患者，447名认知健康对照）。通过沿纤维束的统计分析，我们评估了淀粉样蛋白、tau蛋白和APOE基因变异对大脑神经通路的局部影响。BUAN可量化白质纤维束的微观结构特性，支持沿纤维束的统计分析，以识别与脑微观结构相关的因素。我们可视化了阿尔茨海默病中白质纤维束与tau蛋白和淀粉样蛋白负荷的三维关系；皮质附近的强关联可能支持疾病沿神经通路传播的模型。相对于中性基因型APOE ϵ3/ϵ3，携带AD风险的APOE ϵ4基因型携带者表现出微观结构异常，而携带保护性ϵ2基因型的携带者也表现出细微差异。在所有微观结构指标中，平均扩散率（MD）通常与AD病理学表现出最强的关联，其次是轴向扩散率（AxD）和径向扩散率（RD），而各向异性分数（FA）通常是最不敏感的指标。沿纤维束的微观结构指标对tau蛋白和淀粉样蛋白积累敏感，显示出扩散MRI追踪AD病理学并描绘其对神经通路影响的潜力。
