Locus coeruleus imaging as a biomarker for noradrenergic dysfunction in neurodegenerative diseases
Locus coeruleus imaging as a biomarker for noradrenergic dysfunction in neurodegenerative diseases
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DOI：
10.1093/brain/awz193
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发表时间：
2019-09-01
期刊：
影响因子：
14.5
通讯作者：
Haemmerer, Dorothea
中科院分区：
文献类型：
--
作者：
Betts, Matthew J.;Kirilina, Evgeniya;Haemmerer, Dorothea
蓝斑是脑中去甲肾上腺素的主要来源，在神经退行性疾病的早期阶段，蓝斑的病理变化在组织学上是明显的。新的MRI方法现在提供了一个机会，量化蓝斑在体内疾病进展过程中的结构特征。结合神经病理学生物标志物，体内蓝斑成像可以帮助了解蓝斑神经变性对阿尔茨海默病，非典型神经退行性痴呆和帕金森病的临床和病理表现的贡献。此外，由于去甲肾上腺素能系统的功能敏感性可能会随着疾病的进展而改变，蓝斑完整性的体内测量可以为认知和行为症状提供新的病理生理学见解。蓝斑成像也有望根据去甲肾上腺素能功能障碍将患者分为临床试验。在这篇文章中，我们提出了一个共识，如何在体内评估蓝斑完整性的非侵入性可用于神经退行性疾病的临床研究。我们概述了体内、死后和临床研究的下一步，这些研究可以为评估蓝斑成像作为神经退行性疾病生物标志物的潜力奠定基础。
Pathological alterations to the locus coeruleus, the major source of noradrenaline in the brain, are histologically evident in early stages of neurodegenerative diseases. Novel MRI approaches now provide an opportunity to quantify structural features of the locus coeruleus in vivo during disease progression. In combination with neuropathological biomarkers, in vivo locus coeruleus imaging could help to understand the contribution of locus coeruleus neurodegeneration to clinical and pathological manifestations in Alzheimer's disease, atypical neurodegenerative dementias and Parkinson's disease. Moreover, as the functional sensitivity of the noradrenergic system is likely to change with disease progression, in vivo measures of locus coeruleus integrity could provide new pathophysiological insights into cognitive and behavioural symptoms. Locus coeruleus imaging also holds the promise to stratify patients into clinical trials according to noradrenergic dysfunction. In this article, we present a consensus on how non-invasive in vivo assessment of locus coeruleus integrity can be used for clinical research in neurodegenerative diseases. We outline the next steps for in vivo, post-mortem and clinical studies that can lay the groundwork to evaluate the potential of locus coeruleus imaging as a biomarker for neurodegenerative diseases.