Plaquing up the works Juan Gaertner/Science Photo Library

Our brain’s defence against invading microbes could cause Alzheimer’s disease – which suggests that vaccination could prevent the condition.

Alzheimer’s disease has long been linked to the accumulation of sticky plaques of beta-amyloid proteins in the brain, but the function of plaques has remained unclear. “Does it play a role in the brain, or is it just garbage that accumulates,” asks Rudolph Tanzi of Harvard Medical School.

Now he has shown that these plaques could be defences for trapping invading pathogens.


Working with Robert Moir at the Massachusetts General Hospital in Boston, Tanzi’s team has shown that beta-amyloid can act as an anti-microbial compound, and may form part of our immune system.

To test whether beta-amyloid defends us against microbes that manage to get into the brain, the team injected bacteria into the brains of mice that had been bred to develop plaques like humans do. Plaques formed straight away.

“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.”

Double-edged sword

This suggests that infections could be triggering the formation of plaques. These sticky plaques may trap and kill bacteria, viruses or other pathogens, but if they aren’t cleared away fast enough, they may 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.

“This work is really important for showing that amyloid can be related to infection,” says Brian Balin at the Philadelphia College of Osteopathic Medicine in Pennsylvania. His work has implicated Chlamydia pneumoniae as a possible trigger for beta-amyloid formation, and other research has implicated the herpes virus. But until now, there has been no good explanation for why the plaques form and accumulate.

Support for the immune defence idea comes from work by Jacobus Jansen of Maastricht University in the Netherlands. Using MRI brain scans, his team has found that people in the early stages of Alzheimer’s disease have more permeable blood-brain barriers, suggesting that they may have developed the disease because their brains were more vulnerable to attack. “The microbe hypothesis seems plausible,” says Jansen.

If infectious agents are kicking off the formation of plaques, then vaccines could head them off. “You could vaccinate against those pathogens, and potentially prevent this problem arising later in life,” says Moir.

If many microbes are involved, immunising against them all will be hard, says Jansen. “But if the frequency of certain pathogens is quite high, there might be a possibility.”

It won’t be easy though. Balin says developing vaccines against herpes and chlamydia has proven difficult. “People have been trying for many years now.”

Journal reference: Science Translation Medicine, DOI: 10.1126/scitranslmed.aaf1059; Radiology, DOI: 10.1148/radiol.2016152244