What's That (Blue) Spot on my MRI? Multimodal Neuroimaging of the Locus Coeruleus in Neurodegenerative Disease.
What's That (Blue) Spot on my MRI? Multimodal Neuroimaging of the Locus Coeruleus in Neurodegenerative Disease.
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DOI：
10.3389/fnins.2020.583421
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发表时间：
2020
影响因子：
4.3
通讯作者：
Weinshenker D
中科院分区：
文献类型：
--
作者：
Kelberman M;Keilholz S;Weinshenker D
蓝斑（LC）在阿尔茨海默病（AD）、帕金森病（PD）和其他神经退行性疾病的病理生理学中的作用长期以来被低估。虽然AD和PD在临床表现上不同，但两者的特征均为LC中的前驱蛋白聚集、LC的晚期变性和指示LC功能障碍的共病状况。由于LC的体积小且位于脑干深处，许多早期研究仅限于死后组织学技术。因此，人们越来越关注利用LC的体内成像作为临床前神经退行性过程的预测因子和疾病进展的生物标志物。同时，在神经退行性疾病的动物模型中的神经成像有望识别LC回路的早期改变，但迄今为止尚未得到充分利用。虽然仍处于起步阶段，但少数研究报告了单基因突变和病理学对疾病中LC功能的影响，使用各种神经影像学技术。此外，结合成像和光遗传学或化学遗传学允许响应于LC活性的变化来询问网络连接。本文的目的有两个：（1）回顾磁共振成像（MRI）和正电子发射断层扫描（PET）揭示了神经退行性疾病中LC功能障碍及其作为人类生物标志物的潜力，以及（2）探索如何使用动物模型来检验来自临床数据的假设，并建立一个机制框架，以告知LC-集中治疗干预，以缓解症状和阻止疾病进展。
The locus coeruleus (LC) has long been underappreciated for its role in the pathophysiology of Alzheimer’s disease (AD), Parkinson’s disease (PD), and other neurodegenerative disorders. While AD and PD are distinct in clinical presentation, both are characterized by prodromal protein aggregation in the LC, late-stage degeneration of the LC, and comorbid conditions indicative of LC dysfunction. Many of these early studies were limited to post-mortem histological techniques due to the LC’s small size and location deep in the brainstem. Thus, there is a growing interest in utilizing in vivo imaging of the LC as a predictor of preclinical neurodegenerative processes and biomarker of disease progression. Simultaneously, neuroimaging in animal models of neurodegenerative disease holds promise for identifying early alterations to LC circuits, but has thus far been underutilized. While still in its infancy, a handful of studies have reported effects of single gene mutations and pathology on LC function in disease using various neuroimaging techniques. Furthermore, combining imaging and optogenetics or chemogenetics allows for interrogation of network connectivity in response to changes in LC activity. The purpose of this article is twofold: (1) to review what magnetic resonance imaging (MRI) and positron emission tomography (PET) have revealed about LC dysfunction in neurodegenerative disease and its potential as a biomarker in humans, and (2) to explore how animal models can be used to test hypotheses derived from clinical data and establish a mechanistic framework to inform LC-focused therapeutic interventions to alleviate symptoms and impede disease progression.
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DOI：
10.1073/pnas.0700293104
发表时间：
2007-03-20
影响因子：
11.1
作者：
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通讯作者：
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作者：
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影响因子：
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通讯作者：
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影响因子：
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