INTRODUCTIONTypical MRI measures of neurodegeneration have limited sensitivity in early disease stages. Diffusion MRI (dMRI) microstructural measures may allow for detection in preclinical stages.METHODSParticipants had dMRI and either beta‐amyloid PET or plasma biomarkers of Alzheimer's pathology within 18 months of MRI. Microstructure was measured in portions of the medial temporal lobe (MTL) with high neurofibrillary tangle (NFT) burden based on a previously developed post mortem 3D‐map. Regressions examined relationships between microstructure and markers of Alzheimer's pathology in preclinical disease and then across disease stages.RESULTSThere was higher isometric volume fraction in amyloid‐positive compared to amyloid‐negative cognitively unimpaired individuals in high tangle MTL regions. Similarly, plasma biomarkers and 18F‐flortaucipir were associated with microstructural changes in preclinical disease. Additional microstructural effects were seen across disease stages.DISCUSSIONCombining a post mortem atlas of NFT pathology with microstructural measures allows for detection of neurodegeneration in preclinical Alzheimer's disease.Highlights Typical markers of neurodegeneration are not sensitive in preclinical Alzheimer's. dMRI measured microstructure in regions with high NFT. Microstructural changes occur in medial temporal regions in preclinical disease. Microstructural changes occur in other typical Alzheimer's regions in later stages. Combining post mortem pathology atlases with in vivo MRI is a powerful framework.

中文翻译：

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阿尔茨海默病临床前的内侧颞叶灰质微结构


简介神经退行性变的典型 MRI 测量在疾病早期阶段的敏感性有限。弥散 MRI (dMRI) 微观结构测量可能允许在临床前阶段进行检测。方法参与者在 MRI 的 18 个月内进行 dMRI 和 β-淀粉样蛋白 PET 或阿尔茨海默病病理学的血浆生物标志物。根据先前开发的尸检 3D 图，对具有高神经原纤维缠结 (NFT) 负担的内侧颞叶 (MTL) 部分的微观结构进行了测量。回归分析了阿尔茨海默病临床前疾病以及疾病阶段的微观结构和病理标志物之间的关系。结果在高缠结 MTL 区域，与淀粉样蛋白阴性的认知未受损个体相比，淀粉样蛋白阳性的个体具有更高的等距体积分数。同样，血浆生物标志物和 18F-flortaucipir 与临床前疾病的微观结构变化相关。在整个疾病阶段都观察到了额外的微观结构影响。讨论将 NFT 病理学的死后图谱与微观结构测量相结合，可以检测临床前阿尔茨海默病的神经变性。亮点神经变性的典型标志物在临床前阿尔茨海默病中不敏感。 dMRI 测量了高 NFT 区域的微观结构。临床前疾病的内侧颞区发生微观结构变化。其他典型阿尔茨海默病区域在后期也会发生微观结构变化。将死后病理图谱与体内 MRI 相结合是一个强大的框架。