Wu Junjie, Shahid Syed S, Lin Qixiang, Hone-Blanchet Antoine, Smith Jeremy L, Risk Benjamin B, Bisht Aditya S, Loring David W, Goldstein Felicia C, Levey Allan I, Lah James J, Qiu Deqiang
Department of Radiology and Imaging Sciences, Emory University School of Medicine, Atlanta, GA, United States.
Department of Neurology, Emory University School of Medicine, Atlanta, GA, United States.
Front Aging Neurosci. 2022 Aug 12;14:901140. doi: 10.3389/fnagi.2022.901140. eCollection 2022.
While hippocampal atrophy and its regional susceptibility to Alzheimer's disease (AD) are well reported at late stages of AD, studies of the asymptomatic stage of AD are limited but could elucidate early stage pathophysiology as well as provide predictive biomarkers. In this study, we performed multi-modal magnetic resonance imaging (MRI) to estimate morphometry, functional connectivity, and tissue microstructure of hippocampal subfields in cognitively normal adults including those with asymptomatic AD. High-resolution resting-state functional, diffusion and structural MRI, cerebral spinal fluid (CSF), and neuropsychological evaluations were performed in healthy young adults (HY: = 40) and healthy older adults with negative (HO-: = 47) and positive (HO+ : = 25) CSF biomarkers of AD. Morphometry, functional connectivity, and tissue microstructure were estimated from the structural, functional, and diffusion MRI images, respectively. Our results indicated that normal aging affected morphometry, connectivity, and microstructure in all hippocampal subfields, while the subiculum and CA1-3 demonstrated the greatest sensitivity to asymptomatic AD pathology. Tau, rather than amyloid-β, was closely associated with imaging-derived synaptic and microstructural measures. Microstructural metrics were significantly associated with neuropsychological assessments. These findings suggest that the subiculum and CA1-3 are the most vulnerable in asymptomatic AD and tau level is driving these early changes.
虽然在阿尔茨海默病（AD）晚期，海马萎缩及其对AD的区域易感性已有充分报道，但对AD无症状阶段的研究有限，不过这些研究可以阐明早期病理生理学，并提供预测性生物标志物。在本研究中，我们进行了多模态磁共振成像（MRI），以评估认知正常成年人（包括无症状AD患者）海马亚区的形态学、功能连接和组织微观结构。对健康年轻成年人（HY：n = 40）以及脑脊液（CSF）生物标志物为阴性（HO-：n = 47）和阳性（HO+：n = 25）的健康老年人进行了高分辨率静息态功能、扩散和结构MRI、脑脊液检查以及神经心理学评估。分别从结构、功能和扩散MRI图像中评估形态学、功能连接和组织微观结构。我们的结果表明，正常衰老会影响所有海马亚区的形态学、连接性和微观结构，而海马下脚和CA1-3对无症状AD病理表现出最大的敏感性。tau蛋白而非淀粉样β蛋白与成像衍生的突触和微观结构指标密切相关。微观结构指标与神经心理学评估显著相关。这些发现表明，海马下脚和CA1-3在无症状AD中最易受损，tau蛋白水平驱动了这些早期变化。
