Laboratory of FMRI Technology (LOFT), USC Stevens Neuroimaging and Informatics Institute, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA; Department of Neurology, University of Southern California, Los Angeles, CA, USA.
Department of Neurology, University of Southern California, Los Angeles, CA, USA; Alzheimer's Disease Research Center, University of Southern California, Los Angeles, CA, USA.
Neuroimage Clin. 2017 Dec 6;17:751-760. doi: 10.1016/j.nicl.2017.12.003. eCollection 2018.
Autosomal dominant Alzheimer's disease (ADAD) is a small subset of Alzheimer's disease that is genetically determined with 100% penetrance. It provides a valuable window into studying the course of pathologic processes that leads to dementia. Arterial spin labeling (ASL) MRI is a potential AD imaging marker that non-invasively measures cerebral perfusion. In this study, we investigated the relationship of cerebral blood flow measured by pseudo-continuous ASL (pCASL) MRI with measures of cerebral metabolism (FDG PET) and amyloid deposition (Pittsburgh Compound B (PiB) PET). Thirty-one participants at risk for ADAD (age 39 ± 13 years, 19 females) were recruited into this study, and 21 of them received both MRI and FDG and PiB PET scans. Considerable variability was observed in regional correlations between ASL-CBF and FDG across subjects. Both regional hypo-perfusion and hypo-metabolism were associated with amyloid deposition. Cross-sectional analyses of each biomarker as a function of the estimated years to expected dementia diagnosis indicated an inverse relationship of both perfusion and glucose metabolism with amyloid deposition during AD development. These findings indicate that neurovascular dysfunction is associated with amyloid pathology, and also indicate that ASL CBF may serve as a sensitive early biomarker for AD. The direct comparison among the three biomarkers provides complementary information for understanding the pathophysiological process of AD.
常染色体显性阿尔茨海默病（ADAD）是一种遗传决定的、具有 100%外显率的阿尔茨海默病的小部分亚型。它为研究导致痴呆的病理过程提供了一个有价值的窗口。动脉自旋标记（ASL）MRI 是一种潜在的 AD 成像标志物，可无创性测量脑灌注。在这项研究中，我们研究了通过假性连续 ASL（pCASL）MRI 测量的脑血流与脑代谢（FDG PET）和淀粉样蛋白沉积（匹兹堡化合物 B（PiB）PET）测量值之间的关系。这项研究招募了 31 名有 ADAD 风险的参与者（年龄 39±13 岁，19 名女性），其中 21 名参与者接受了 MRI 和 FDG 和 PiB PET 扫描。在研究对象之间，ASL-CBF 与 FDG 之间的区域相关性存在相当大的差异。局部低灌注和低代谢均与淀粉样蛋白沉积有关。每个生物标志物作为预计痴呆诊断时间的函数的横断面分析表明，在 AD 发展过程中，灌注和葡萄糖代谢与淀粉样蛋白沉积呈负相关。这些发现表明神经血管功能障碍与淀粉样蛋白病理学有关，并且还表明 ASL CBF 可能作为 AD 的敏感早期生物标志物。三种生物标志物之间的直接比较为理解 AD 的病理生理过程提供了互补信息。
