Brain’s Circulatory System Clears Waste

A previously unobserved system of channels surrounding brain blood vessels pumps cerebrospinal fluid (CSF) throughout the brain, delivers nutrients, and removes waste—including amyloid-β, the protein whose buildup in the brain is a hallmark of Alzheimer’s disease (Sci. Transl. Med., DOI: 10.1126/scitranslmed.3003748). The work, from Maiken Nedergaard and Jeffrey J. Iliff at the University of Rochester Medical Center and their colleagues, suggests that this long-suspected, but now verified, system holds Alzheimer’s pathology clues and could be harnessed for potential treatments. Modern two-photon microscopy made the research possible, because the circulation is observable only in live animals. The group injected fluorescent dyes into both the blood and CSF systems in live mice. They then observed in real time the flow of CSF into and out of the brain through channels. These channels are composed of parts of workhorse glial cells, which form a sheath around blood vessels. CSF travels along these pathways, then seeps throughout the brain through water channels known as aquaporin-4, then backs out along draining veins. The solute-clearing ability of genetically engineered mice lacking aquaporin-4 dropped by 70%, as did their ability to clear amyloid-β.