A notorious biochemical villain has just revealed its heroic side. Beta-amyloid, a misfolded protein fragment blamed for killing brain cells in Alzheimer’s disease, has reversed the symptoms of mice suffering from the rodent equivalent of multiple sclerosis (MS).

MS occurs when the immune system mistakenly attacks the fatty myelin sheaths around nerve fibres that serve as electrical insulation. Without this insulation, nervous impulses falter, leading to physical and cognitive problems. Myelin increases the speed at which electrical impulses travel around the body.

As it is destroyed, nerve communication falters, leading to physical and cognitive problems. Lawrence Steinman of Stanford University in California had expected amyloid-beta to exacerbate this damage, given that it is toxic to neurons and builds up where myelin sheaths are being destroyed.

However, when his PhD student Jacqueline Grant injected beta-amyloid into the body cavities of mice whose immune systems had been made to attack myelin, it delayed the onset of paralysis, or even reversed it.


At first Steinman thought there must have been some mistake – perhaps the animals’ cages had been mixed up. “It was a creepy, unexpected result,” he says.

But when Grant repeated the experiments, she found exactly the same thing. The injections of beta-amyloid also seemed to reduce circulating levels of immune-signalling molecules involved in inflammation.

In subsequent experiments, Steinman’s team took immune cells from the spleen and lymph nodes of mice treated with beta-amyloid. When the researchers injected these cells into other mice with the MS-like disease, it again reduced their symptoms.

Taken together, these results suggest that beta-amyloid may be able to combat MS by damping down the autoimmune reactions that are the disease’s hallmark.

Although Steinman’s team found no evidence that beta-amyloid built up in the brains of their mice, drug regulators will be wary of any treatment involving a protein implicated in Alzheimer’s disease – especially since other researchers have suggested that beta-amyloid can transfer from the blood into the brain.

Using beta-amyloid itself shouldn’t be necessary, however. In unpublished work, Steinman’s team has found that a protein called alpha-crystallin B – found in large quantities in the lens of the eye – has similar effects. Like other amyloid proteins, it accumulates in parallel sheets, but seems to be benign.

The finding that different amyloid proteins can have the same immune-damping effect makes good sense to Charles Glabe of the University of California, Irvine, who studies the proteins’ role in neurodegenerative diseases. Although different amyloid proteins have different sequences of amino acids, they may look the same to the immune system, he suggests: “The structures are so similar.”

Still, Steinman warns that curing mice with an MS-like condition is just the first step on a long and potentially bumpy road to developing a therapy for people with the disease.

Journal reference: Science Translational Medicine, DOI: 10.1126/scitranslmed.3004145