阿尔茨海默病连续体中白质纤维束对淀粉样蛋白病理学的易损性。
White Matter Tract Vulnerability to Amyloid Pathology on the Alzheimer's Disease Continuum.
作者信息
Chandio Bramsh Qamar, Nir Talia M, Villalon-Reina Julio E, Thomopoulos Sophia I, Feng Yixue, Reid Robert I, Jack Clifford R, Weiner Michael W, Garyfallidis Eleftherios, Jahanshad Neda, Braskie Meredith N, O'Bryant Sid, Thompson Paul M
机构信息
Imaging Genetics Center, Mark and Mary Stevens Neuroimaging and Informatics Institute, Keck School of Medicine, University of Southern California, Marina del Rey, CA, USA.
Department of Radiology, Mayo Clinic, Rochester, MN, United States.
出版信息
bioRxiv. 2025 Aug 19:2025.08.18.670970. doi: 10.1101/2025.08.18.670970.
Alzheimer's disease (AD) is marked by progressive cognitive decline and memory loss, due to the abnormal accumulation of amyloid-beta () plaques, followed by tau pathology, and a gradually spreading pattern of neuronal loss. Understanding how amyloid positivity affects the brain's neural pathways is critical for understanding how the brain changes with AD pathology. Tractometry offers a powerful approach for the , 3D quantitative assessment of white matter tracts, enabling the localization of microstructural abnormalities in diseased populations and those at risk. In this study, we applied BUAN (Bundle Analytics) tractometry to multi-cohort diffusion MRI data from a total of 1,908 participants: 606 participants in ADNI3 (Alzheimer's Disease Neuroimaging Initiative Phase 3) and 1,302 participants from the HABS-HD (Health and Aging Brain Study-Healthy Diversity). Using BUAN and along-tract statistical analysis, we assessed the localized effects of amyloid positivity, potentially mediated by tau, on white matter pathways, with amyloid positivity quantified via amyloid-sensitive positron emission tomography (PET). BUAN enables tract-specific quantification of white matter microstructure and supports statistical testing along the full length of fiber bundles to detect subtle, spatially localized associations. We present 3D visualizations of tract-wise amyloid associations, highlighting distinct patterns of white matter degeneration in AD.
阿尔茨海默病(AD)的特征是进行性认知衰退和记忆丧失,这是由于β淀粉样蛋白(Aβ)斑块异常积累,随后出现tau病理改变,以及神经元逐渐扩散性丧失。了解淀粉样蛋白阳性如何影响大脑神经通路对于理解大脑如何随AD病理变化至关重要。纤维束成像提供了一种强大的方法,用于对白质纤维束进行三维定量评估,能够在患病群体和有风险的人群中定位微观结构异常。在本研究中,我们将纤维束分析(BUAN)应用于来自总共1908名参与者的多队列扩散磁共振成像(MRI)数据:阿尔茨海默病神经成像计划第三阶段(ADNI3)中的606名参与者以及健康与衰老大脑研究 - 健康多样性(HABS - HD)中的1302名参与者。使用BUAN和沿纤维束的统计分析,我们通过对淀粉样蛋白敏感的正电子发射断层扫描(PET)量化淀粉样蛋白阳性,评估了可能由tau介导的淀粉样蛋白阳性对白质通路的局部影响。BUAN能够对白质微观结构进行纤维束特异性量化,并支持沿纤维束全长进行统计测试,以检测细微的、空间局部化的关联。我们展示了纤维束方向淀粉样蛋白关联的三维可视化结果,突出了AD中白质变性的不同模式。