蓝斑(LC),脑干中的微小核和去甲肾上腺素合成的主要部位,在调节自主神经功能方面有重要作用,唤醒,注意,和神经炎症。LC功能障碍与一系列疾病有关;然而,它在阿尔茨海默氏病(AD)中的作用引起了特别的兴趣。LC在AD中经历显著的神经元丢失,认为发生在疾病过程的早期。虽然LC中的神经元丢失也被认为发生在衰老中,这种关系不太清楚,因为调查结果是矛盾的。已建议LC密度指示认知储备,并将讨论这些主张的证据。最近的成像技术允许使用神经黑色素敏感的MRI在体内可视化LC,正在发展我们对LC在衰老和AD中的作用的理解。在大多数个体中,LC中的Tau病理学在早期就很明显;然而,tau积累与神经元丢失之间的关系以及为什么一些个体随后发展为AD尚不清楚。神经黑色素色素随着年龄的增长在LC细胞内积累,被认为在释放到细胞外环境中时是有毒和炎性的。这篇综述将探讨我们目前对死后衰老和AD的LC变化的认识,成像,和实验研究。我们将讨论LC对神经元丢失的易感性背后的原因,重点研究了细胞外神经黑色素的作用和由LC-去甲肾上腺素途径功能障碍引起的神经炎症。
The locus coeruleus (LC), a tiny nucleus in the brainstem and the principal site of noradrenaline synthesis, has a major role in regulating autonomic function, arousal, attention, and neuroinflammation. LC dysfunction has been linked to a range of disorders; however particular interest is given to the role it plays in Alzheimer\'s disease (AD). The LC undergoes significant neuronal loss in AD, thought to occur early in the disease process. While neuronal loss in the LC has also been suggested to occur in aging, this relationship is less clear as the findings have been contradictory. LC density has been suggested to be indicative of cognitive reserve and the evidence for these claims will be discussed. Recent imaging techniques allowing visualization of the LC in vivo using
neuromelanin-sensitive MRI are developing our understanding of the role of LC in aging and AD. Tau pathology within the LC is evident at an early age in most individuals; however, the relationship between tau accumulation and neuronal loss and why some individuals then develop AD is not understood.
Neuromelanin pigment accumulates within LC cells with age and is proposed to be toxic and inflammatory when released into the extracellular environment. This
review will explore our current knowledge of the LC changes in both aging and AD from postmortem, imaging, and experimental studies. We will discuss the reasons behind the susceptibility of the LC to neuronal loss, with a focus on the role of extracellular
neuromelanin and neuroinflammation caused by the dysfunction of the LC-noradrenaline pathway.