Fight Aging!

While the immune system of the brain is distinct from that of the rest of the body, the central nervous system walled off by the blood-brain barrier, the inflammatory status of the brain is very much influenced by the inflammatory status of the rest of the body. Signals pass back and forth, and at the edges of the brain there are a variety of tissues in which one can find peripheral immune cells such as macrophages of the innate immune system or T cells of the adaptive immune system.

One such tissue is the meninges, the membranes that wrap the brain and spinal cord. In recent years, since the discovery of the glymphatic system that drains waste from the brain, more attention has been given to cell populations in the lymphatic vessels and vasculature of the meninges, as well as other tissues bordering the brain, such as the choroid plexus. As an example of this work, today's open access review discusses what is known of the way in which peripheral immune system involvement in the meninges may influence the inner regions of the brain.

Current views on meningeal lymphatics and immunity in aging and Alzheimer's disease

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 cells 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 central nervous system, 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 central nervous system fluid and macromolecule drainage, meningeal and brain immunity, as well as glial and neuronal function in aging and in AD.