Neurodegenerative diseases like Alzheimer's and Parkinson's are often caused by the accumulation of harmful protein clusters in the brain. While researchers have been trying to develop treatments that target these toxic clusters to alleviate these conditions, progress has been slow.
Scientists at the Washington University School of Medicine in St. Louis have identified a potential new method for enhancing the clearance of waste from the brain, which could have implications for the treatment or prevention of neurodegenerative diseases. They discovered that immune cells surrounding the brain can affect the efficiency of waste removal and that these immune cells become impaired in old mice, as well as in mice and humans with Alzheimer's disease.
Treating Neurodegenerative Diseases
Furthermore, they found that administering an immune-stimulating compound to old mice can rejuvenate these immune cells and improve the brain's ability to clear waste. According to a recent study published in the journal Nature, researchers at the Washington University School of Medicine have found that immune cells surrounding the brain may hold the key to treating or preventing neurodegenerative diseases. These cells, which become impaired with age and in conditions like Alzheimer's disease, can be rejuvenated by treatment with an immune-stimulating compound, improving waste clearance from the brain and offering a potential new approach to age-related brain diseases.
As senior author Jonathan Kipnis explained, while it may not be possible to revive damaged neurons, targeting immune cells on the periphery of the brain could be a more feasible option for treatment, as they are more accessible and can be "drugged or replaced." Jonathan Kipnis is a leading expert in the field of neuroimmunology, which investigates the relationship between the immune system and the brain in both healthy and diseased states.
In 2015, he discovered a system of vessels that transport fluid, immune cells, and small molecules from the brain to the lymph nodes, where many immune cells are located. In the following year, he and his team demonstrated that certain experimental Alzheimer's therapies were more effective in mice when combined with a treatment that promotes the drainage of fluid and debris from the brain, as reported by SciTech Daily.
In this study, Jonathan Kipnis and Antoine Drieu, the lead author and a postdoctoral researcher, respectively, aimed to understand the role of immune cells located along the blood vessels of the brain and in the leptomeninges, the tissues surrounding the brain and spinal cord. These cells, known as parenchymal border macrophages, are situated at the boundary between cerebrospinal fluid and brain tissue.
Study's Revelation
By studying mice, Kipnis, Drieu, and their team discovered that parenchymal border macrophages regulate the movement of blood vessels, which in turn controls the flow of fluid through the brain. When these macrophages were either reduced in number or impaired, debris accumulated in the brain. Drieu stated that cerebrospinal fluid flow is impaired in several neurodegenerative conditions, including Alzheimer's, stroke, Parkinson's, and multiple sclerosis, and that increasing the number or function of these macrophages might be a way to slow the progression of these diseases. While this is a promising possibility, more research is needed to determine if this approach would be effective.
Further investigation revealed that parenchymal border macrophages are altered in people with Alzheimer's disease and mice with an Alzheimer's-like condition. These immune cells are less able to consume and dispose of waste and are less effective at regulating fluid flow.
Kipnis, Drieu, and their team found that as people and mice age, brain fluid flow decreases and that the type of parenchymal border macrophage most important for waste clearance and fluid flow becomes less common in older mice. When they treated older mice with a protein that activates macrophage activity, the border macrophages behaved more like those in younger mice, improving fluid flow and waste clearance in the brain.
Such results suggest that parenchymal border macrophages may be a target for pharmacological intervention to alleviate brain clearance deficits associated with aging and Alzheimer's disease. Kipnis is considering how these cells could be replaced or rejuvenated in aging brains and as a treatment for Alzheimer's, with the hope of slowing or delaying the onset of age-related brain diseases.
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