Comment; A greater appreciate of the interplay between the BBB & Glymphatic system is occuring. It’ll be interesting to further define activity of the immune system in this process as well. We’ve already established that the brain is not as sterile as we thought, nucleic acid probes show that there are commensual bacteria permitted to exist within the brain–what is THEIR role?
Verheggen ICM1, Van Boxtel MPJ2, Verhey FRJ2, Jansen JFA3, Backes WH3.
Author information
1School for Mental Health and Neuroscience/ Alzheimer Centrum Limburg, Department of Psychiatry & Neuropsychology, Maastricht University, P.O. Box 616, 6200 MD, Maastricht, The Netherlands. Electronic address: inge.verheggen@maastrichtuniversity.nl.2School for Mental Health and Neuroscience/ Alzheimer Centrum Limburg, Department of Psychiatry & Neuropsychology, Maastricht University, P.O. Box 616, 6200 MD, Maastricht, The Netherlands.3School for Mental Health and Neuroscience, Department of Radiology & Nuclear Medicine, Maastricht University Medical Center, P.O. Box 5800, 6202 AZ, Maastricht, The Netherlands.
Abstract
Neurovascular pathology concurs with protein accumulation, as the brain vasculature is important for waste clearance. Interstitial solutes, such as amyloid-β, were previously thought to be primarily cleared from the brain by blood-brain barrier transport. Recently, the glymphatic system was discovered, in which cerebrospinal fluid is exchanged with interstitial fluid, facilitated by the aquaporin-4 water channels on the astroglial endfeet. Glymphatic flow can clear solutes from the interstitial space. Blood-brain barrier transport and glymphatic clearance likely serve complementary roles with partially overlapping mechanisms providing a well-conditioned neuronal environment. Disruption of these mechanisms can lead to protein accumulation and may initiate neurodegenerative disorders, for instance amyloid-β accumulation and Alzheimer’s disease. Although both mechanisms seem to have a similar purpose, their interaction has not been clearly discussed previously. This review focusses on this interaction in healthy and pathological conditions. Future health initiatives improving waste clearance might delay or even prevent onset of neurodegenerative disorders. Defining glymphatic flow kinetics using imaging may become an alternative way to identify those at risk of Alzheimer’s disease.
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