Researchers report that the blood-brain barrier selectively carries proteins into the brain, that this transport changes in Alzheimer’s-like mice, and that raising the liver-made protein APOA1 eased brain and behavioral problems in the animals.
In the Cell study, the team tracked 861 blood proteins in mice and found that 92 crossed into brain tissue. Many of these proteins came from organs such as the liver. The team also found that imported proteins reached particular types of brain cells.
This suggests the barrier does more than keep substances out. It also helps direct signals and other molecules from the body. APOA1 was delivered to astrocytes, which are support cells in the brain.
Another liver protein, SERPINA1, was taken up by microglia, immune cells that live in the brain. In 5xFAD mice, a model of Alzheimer’s disease, uptake of APOA1 and two other proteins fell. Uptake of four other proteins, including SERPINA1, increased.
This indicated that the changes were selective rather than a general failure of the barrier. The team then increased APOA1 production in the liver. This restored APOA1 in the brain and improved problems involving astrocytes, synapses and behavior in the mice.
The results do not show that the same transport changes happen in people. They also do not show that APOA1 would treat Alzheimer’s disease in humans. Still, the findings suggest that studying the barrier’s role in moving proteins could open a new way to investigate brain disease.