Locus coeruleus (LC) is the main noradrenergic (NA) nucleus of the central nervous system. LC degenerates early during Alzheimer's disease (AD) and NA loss might concur to AD pathogenesis. Aside from neurons, LC terminals provide dense innervation of brain intraparenchymal arterioles/capillaries, and NA modulates astrocyte functions. The term neurovascular unit (NVU) defines the strict anatomical/functional interaction occurring between neurons, glial cells, and brain vessels. NVU plays a fundamental role in coupling the energy demand of activated brain regions with regional cerebral blood flow, it includes the blood–brain barrier (BBB), plays an active role in neuroinflammation, and participates also to the glymphatic system. NVU alteration is involved in AD pathophysiology through several mechanisms, mainly related to a relative oligoemia in activated brain regions and impairment of structural and functional BBB integrity, which contributes also to the intracerebral accumulation of insoluble amyloid. We review the existing data on the morphological features of LC‐NA innervation of the NVU, as well as its contribution to neurovascular coupling and BBB proper functioning. After introducing the main experimental data linking LC with AD, which have repeatedly shown a key role of neuroinflammation and increased amyloid plaque formation, we discuss the potential mechanisms by which the loss of NVU modulation by LC might contribute to AD pathogenesis. Surprisingly, thus far not so many studies have tested directly these mechanisms in models of AD in which LC has been lesioned experimentally. Clarifying the interaction of LC with NVU in AD pathogenesis may disclose potential therapeutic targets for AD.

中文翻译：

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蓝斑和神经血管单元：从它在生理学中的作用到它在阿尔茨海默病发病机制中的潜在作用。

蓝斑核 (LC) 是中枢神经系统的主要去甲肾上腺素能 (NA) 核。LC 在阿尔茨海默病 (AD) 早期退化，NA 丢失可能与 AD 发病机制一致。除了神经元，LC 终端提供脑实质内小动脉/毛细血管的密集神经支配，NA 调节星形胶质细胞的功能。术语神经血管单元 (NVU) 定义了神经元、神经胶质细胞和脑血管之间发生的严格的解剖/功能相互作用。NVU 在将激活的大脑区域的能量需求与局部脑血流耦合方面发挥着重要作用，它包括血脑屏障 (BBB)，在神经炎症中发挥积极作用，并且还参与了淋巴系统。NVU 改变通过多种机制参与 AD 病理生理学，主要与激活的大脑区域的相对低血症和结构和功能 BBB 完整性受损有关，这也有助于不溶性淀粉样蛋白的脑内积聚。我们回顾了关于 NVU 的 LC-NA 神经支配形态特征的现有数据，以及其对神经血管耦合和 BBB 正常功能的贡献。在介绍了将 LC 与 AD 联系起来的主要实验数据后，我们讨论了 LC 对 NVU 调节的丧失可能有助于 AD 发病机制的潜在机制，这些数据反复显示了神经炎症和增加淀粉样蛋白斑块形成的关键作用。令人惊讶的是，到目前为止，还没有多少研究直接在 LC 实验性损伤的 AD 模型中测试这些机制。