University of Tokyo, Niigata U. cut mouse brain tau by 46%

After a drug was administered to mice for three months, abnormal tau proteins accumulated in the hippocampus fell by about 46%. This was confirmed by a research team from the University of Tokyo, Niigata University and other institutions in mice genetically modified to accumulate abnormal tau. Tau in the cerebrospinal fluid more than doubled, suggesting that proteins in the brain may have been carried out of it by the flow of the fluid.

The target was the “glymphatic system,” which flushes waste away through the circulation of cerebrospinal fluid. Astrocytes, cells arranged around blood vessels, contain aquaporin 4 (AQP4), a channel through which water flows. The research team used TGN-073, a drug that activates AQP4, to promote the influx of cerebrospinal fluid and the clearance of abnormal proteins. MRI scans also showed increased cerebrospinal fluid inflow, particularly in the cortex, compared with the control group.

The effects extended beyond the amount of tau. Abnormal tau in the entorhinal and piriform cortices fell by about 37%, while neuronal death and inflammation in the brain were also suppressed. The hippocampus was preserved at about 24% larger than in the control group. By contrast, no beneficial effect was observed in mice lacking AQP4, indicating that the drug’s action depends on this water channel.

There is, however, a major caveat. No improvements in memory or behavior were confirmed after treatment. The findings come from experiments in mice and do not show that the treatment can cure Alzheimer’s disease in humans. The research paper was published in the international academic journal “Molecular Neurodegeneration.”

Whether the same enhancement of clearance occurs in humans, and whether it leads to changes in memory or behavior, remains to be determined.