Researchers at University College London have identified a previously unknown network of tiny channels in the brain that may play a role in removing toxic proteins associated with Alzheimer's disease, according to research described in a new study.
The discovery addresses a significant gap in scientific understanding. Neuroscientist David Attwell explained to ScienceAlert that "the pathways by which toxic proteins are removed from the brain are poorly understood." This knowledge gap complicates research into Alzheimer's disease, which involves the accumulation of amyloid beta and abnormal tau proteins. Understanding why these proteins build up requires investigating both how they are produced and how they are removed from the brain.
The research team used fluorescently labeled tau and amyloid beta proteins to trace the clearance pathways in mice. The labeled proteins moved through channels measuring approximately 2 micrometers across that form an interconnected mesh. These channels extend along blood vessel walls into the membranes covering the brain and along nerves leaving it. In some experiments, tracers reached channels at the brain's upper surface within 7.5 minutes of administration. The researchers identified the channels as likely being formed by fibroblastic reticular cells, similar to cells that build fluid-carrying networks in lymph nodes outside the brain.
The findings suggest two potential exit routes for proteins. Tau traveled through both arteriole walls—small blood vessels supplying brain tissue—and channels around venules, small blood vessels that carry blood away. Measurements indicated roughly similar amounts of protein passed through each route, supporting the possibility that they are part of a shared network. The researchers also found that in mice modeling aspects of Alzheimer's disease, the animals' own naturally produced amyloid beta was present within the channels, suggesting the network transports proteins generated inside the brain rather than only substances introduced during experiments.
To test whether humans possess similar structures, the research team examined brain tissue removed during surgery from five patients being treated for brain tumors. When fluorescently labeled tau and amyloid beta were applied to the human tissue samples, the proteins concentrated in channels resembling those observed in mice, with similar dimensions. However, tissue maintained outside the living body cannot reveal the complete clearance process as it occurs in a living person.
Attwell emphasized an important caveat: "In the future it will be important to demonstrate that these tubes function in the same way in living humans." The study has not undergone peer review, and additional research is needed to establish whether these channels function identically in living humans as they do in laboratory conditions. Other clearance mechanisms may also operate alongside this newly identified network, including the breakdown of proteins within brain tissue and their passage across blood vessel cells into the bloodstream.
The research builds on earlier investigations into how the brain removes waste products. Scientists have previously proposed different routes for protein clearance, including pathways along blood vessel walls and mechanisms explained by the glymphatic system. The identification of this specific cellular structure may help explain how proteins travel through the proposed exit routes already documented by researchers.
