Current views on meningeal lymphatics and immunity in aging and Alzheimer's disease.
Current views on meningeal lymphatics and immunity in aging and Alzheimer's disease.
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脑膜淋巴和免疫在衰老和阿尔茨海默病中的研究进展。
DOI：
10.1186/s13024-023-00645-0
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发表时间：
2023-08-14
影响因子：
15.1
通讯作者：
Da Mesquita, Sandro
中科院分区：
文献类型：
--
作者：
Rego, Shanon;Sanchez, Guadalupe;Da Mesquita, Sandro
关键词：
阿尔茨海默病（AD）是一种与衰老相关的痴呆形式，其与淀粉样蛋白β和神经元缠结的病理性聚集物在脑中的积累相关。这些现象伴随着加剧的炎症和显著的神经元损失，这共同导致了认知能力的加速下降。AD的多因素性质，加上我们对其病因学和病理生理学的有限了解，降低了我们开发AD患者有效治疗方法的能力。在过去的几十年里，全基因组关联研究和生物标志物开发，以及涉及动物模型的机制实验，已经确定了在AD脑病理学调节中发挥关键作用的不同免疫组分，影响其进展和严重程度。正如我们将在这篇综述中所述，最近的大部分努力都是为了更好地理解大脑先天免疫的作用，特别是小胶质细胞。然而，尽管脑驻留免疫细胞内缺乏多样性，但脑边界组织，特别是脑膜，含有相当数量的不同类型和亚型的适应性和先天性免疫细胞。除了在AD研究中占据中心舞台的小胶质细胞外，还有新的令人兴奋的证据表明适应性免疫细胞，即在大脑及其脑膜中发现的T和B细胞，是AD中神经炎症和神经元（dys）功能的重要调节剂。重要的是，真正的和功能性的淋巴管网络存在于大脑周围的最外层脑膜层，硬脑膜。脑膜淋巴管直接连接到不同哺乳动物物种（包括人类）的外周淋巴系统，并通过不仅在脑膜局部而且在脑组织水平形成免疫应答，在保持CNS的“健康”免疫监视中发挥关键作用。在这篇综述中，我们将提供一个全面的看法，我们目前的知识脑膜淋巴管，强调其所描述的作用，在调节中枢神经系统的液体和大分子的排水，脑膜和脑免疫，以及胶质细胞和神经元的功能，在老化和AD。
Alzheimer’s disease (AD) is an aging-related form of dementia associated with the accumulation of pathological aggregates of amyloid beta and neurofibrillary tangles in the brain. These phenomena are accompanied by exacerbated inflammation and marked neuronal loss, which altogether contribute to accelerated cognitive decline. The multifactorial nature of AD, allied to our still limited knowledge of its etiology and pathophysiology, have lessened our capacity to develop effective treatments for AD patients. Over the last few decades, genome wide association studies and biomarker development, alongside mechanistic experiments involving animal models, have identified different immune components that play key roles in the modulation of brain pathology in AD, affecting its progression and severity. As we will relay in this review, much of the recent efforts have been directed to better understanding the role of brain innate immunity, and particularly of microglia. However, and despite the lack of diversity within brain resident immune cells, the brain border tissues, especially the meninges, harbour a considerable number of different types and subtypes of adaptive and innate immune cells. Alongside microglia, which have taken the centre stage as important players in AD research, there is new and exciting evidence pointing to adaptive immune cells, namely T and B cells found in the brain and its meninges, as important modulators of neuroinflammation and neuronal (dys)function in AD. Importantly, a genuine and functional lymphatic vascular network is present around the brain in the outermost meningeal layer, the dura. The meningeal lymphatics are directly connected to the peripheral lymphatic system in different mammalian species, including humans, and play a crucial role in preserving a “healthy” immune surveillance of the CNS, by shaping immune responses, not only locally at the meninges, but also at the level of the brain tissue. In this review, we will provide a comprehensive view on our current knowledge about the meningeal lymphatic vasculature, emphasizing its described roles in modulating CNS fluid and macromolecule drainage, meningeal and brain immunity, as well as glial and neuronal function in aging and in AD.
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影响因子：
13.6
作者：
Da Mesquita S;Herz J;Wall M;Dykstra T;de Lima KA;Norris GT;Dabhi N;Kennedy T;Baker W;Kipnis J
通讯作者：
Kipnis J
影响因子：
82.9
作者：
Benakis C;Brea D;Caballero S;Faraco G;Moore J;Murphy M;Sita G;Racchumi G;Ling L;Pamer EG;Iadecola C;Anrather J
通讯作者：
Anrather J
影响因子：
30.5
作者：
Alves de Lima K;Rustenhoven J;Da Mesquita S;Wall M;Salvador AF;Smirnov I;Martelossi Cebinelli G;Mamuladze T;Baker W;Papadopoulos Z;Lopes MB;Cao WS;Xie XS;Herz J;Kipnis J
通讯作者：
Kipnis J
影响因子：
7.7
作者：
Absinta M;Ha SK;Nair G;Sati P;Luciano NJ;Palisoc M;Louveau A;Zaghloul KA;Pittaluga S;Kipnis J;Reich DS
通讯作者：
Reich DS
影响因子：
5.9
作者：
Bhattacherjee, Abhishek;Rodrigues, Emily;Macauley, Matthew S.
通讯作者：
Macauley, Matthew S.