Plaques in the brain are behind Alzheimer’s Juan Gaertner/Science Photo Library

It’s a double-edged sword. The protein plaques in the brain associated with Alzheimer’s disease could be created as our immune system fights off invading microbes.

Alzheimer’s disease has long been linked to the accumulation of sticky plaques of beta-amyloid proteins in the brain, but their function – if any – has remained unclear.

“Why does beta-amyloid accumulate in people as they get older? Does it play a role in the brain, or is it just garbage that accumulates,” asks Rudolph Tanzi of Harvard Medical School.


Tanzi’s team has been working with Robert Moir at the Massachusetts General Hospital in Boston to look at the protein in other animals. The group has found that a certain sequence of particular amino acids in human beta-amyloid is shared widely – among 70 per cent of vertebrates, including in the coelacanth, an ancient type of fish.

That this sequence is shared so widely, and has not changed over time, suggests there is a reason it has been conserved. “This is a very old peptide doing something that’s important,” says Moir.

Brain defence

Moir had previously found that beta-amyloid kills microbes as well as does an anti-microbial peptide called LL-37. This molecule is a foot soldier for the primitive part of our immune system, which we share with many other animals.

So the team tested whether the purpose of beta-amyloid is also to kill microbes in the brain. When they injected bacteria into the brains of mice bred to be able to develop plaques much as humans do, the mice developed amyloid plaques overnight.

“When you look in the plaques, each one had a single bacterium in it,” says Tanzi. “A single bacterium can induce an entire plaque overnight.”

This suggests that microbial infection could be triggering the formation of plaques that cause Alzheimer’s disease. Somehow, bacteria, viruses or other pathogens may be crossing the blood-brain barrier and getting into the brain. The brain may be responding by using beta-amyloid to trap and kill them. But if these plaques aren’t cleared away fast enough, they may then lead to inflammation and tangles of another protein, called tau, causing neurons to die and the progression towards Alzheimer’s disease.

“The stickiness of amyloid is both a godsend and a curse,” says Samuel Gandy at the Mount Sinai Hospital in New York.

Alzheimer’s vaccination

Other work has suggested that infections can cause Alzheimer’s disease, arguing that microbes lead to inflammation, directly causing neuron death and cognitive decline. Chlamydia and the herpes virus are among the suggested culprits.

But Tanzi and Moir believe it is beta-amyloid that causes the damage, not the microbes themselves.

The team now plans to look at the brains of people who have died from Alzheimer’s disease. If the team finds microbial DNA or RNA inside the plaques, the discovery could open up a new way to think about Alzheimer’s disease and how it might be treated.

“You could vaccinate against those pathogens, and potentially prevent this problem arising later in life,” says Moir.

Journal reference: Science Translational Medicine, DOI: 10.1126/scitranslmed.aaf1059

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