New Delhi: Scientists have discovered that the brain’s protective barrier may contribute to the early development of Alzheimer’s disease by preventing beneficial proteins from entering the brain, according to a new study involving mice.
The researchers identified 92 blood proteins that can cross the blood-brain barrier, a network of cells surrounding blood vessels that regulates what enters the brain in the study published in Cell on 11 November.
Researchers at the Gladstone Institutes in California found that this transport system was disrupted in mice with Alzheimer’s-like disease, even before the barrier began leaking harmful substances.
“The paradigm in the field has been that the blood-brain barrier is normally impermeable and then becomes leaky as a result of Alzheimer’s disease,” study co-author Andrew Yang told Nature.
How the blood-brain barrier works
The blood-brain barrier protects the brain by restricting the movement of potentially harmful substances from the bloodstream.
However, researchers have increasingly recognised that it also transports substances essential for maintaining healthy brain function. To investigate this process, the team developed a method to label and track proteins circulating in the blood of mice.
Of the 861 proteins examined, 191 interacted with the brain’s blood vessels, while 92 crossed the barrier and entered brain tissue. Most originated in organs elsewhere in the body, particularly the liver.
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A protective protein linked to Alzheimer’s
The researchers focused on apolipoprotein A1 (APOA1), a protein produced primarily in the liver.
Once inside the brain, APOA1 stimulates cells called astrocytes to release cholesterol, which helps maintain connections between neurons. The team identified two proteins involved in this process: SR-B1, which helps APOA1 cross the blood-brain barrier, and ABCA1, which helps regulate cholesterol transport in astrocytes.
In mice with Alzheimer’s-like disease, researchers found that the barrier transported less APOA1 into the brain before it developed the leakage commonly associated with advancing disease.
“Before the barrier starts leaking harmful proteins into the brain, it stops letting the beneficial ones through,” lead author Haoyue Zhou said in an official statement.
Could the discovery lead to treatments?
To investigate whether restoring APOA1 could help, researchers genetically modified mice to produce more of the protein in their livers.
The additional APOA1 entered the brain and reduced several signs of Alzheimer’s-like disease, including inflammation and damage to neuronal connections. Yang suggested that Alzheimer’s disease might partly involve a breakdown in communication between the brain and other organs.
However, the findings come from animal experiments and do not establish whether the same process occurs in people with Alzheimer’s disease, as Liyu Chen, a neuroscientist not involved in the study explained to Nature. Further research will be needed to determine whether restoring protein transport across the blood-brain barrier could become a safe and effective treatment in humans.
(Edited by Janaki Pande)