Research: do germs cause Alzheimer's?

The germ of forgetting - The latest findings indicate that infections promote the pathological processes in the brain. Herpes viruses are suspected, but so are bacteria from gum pockets

A look into the brain: In the picture, the typical accumulations of amyloid proteins glow red and yellow

© picture: Alexander Drzezga

Find the germ! This is the motto of a competition organized by the US doctor and publisher Leslie Norins. Anyone who has researched which pathogens cause Alzheimer's disease by the end of 2020 will be rewarded with prize money of one million US dollars. "It is time that the hunt for a microorganism that played the role of the culprit in Alzheimer's disease was more aggressively funded," says Norins.

The initiator is convinced that "most cases of Alzheimer's dementia are caused by a germ that has not yet been identified". And he's not the only one. Three years ago, 33 scientists from all over the world called in the Journal of Alzheimer's Disease to finally research the role of pathogens and to test appropriate therapies on volunteers.

So far, almost all tested active ingredients are directed against certain proteins in the patient's brain - without success. No study has been able to show that Alzheimer's can be stopped in this way.

Viruses in the brain

Already decades before dementia breaks out, the proteins accumulate in the brain: first beta-amyloids, later tau proteins. They are used to diagnose Alzheimer's and to identify the stage of the disease. However, some experts do not consider it to be the cause of the disease, which mainly affects the elderly.

But what speaks in favor of an infection causing Alzheimer's instead? For example, findings from recent years that beta-amyloids that accumulate in the brain of those affected kill viruses and bacteria. Some researchers even believe that proteins are part of our immune system that eliminates pathogens.

Several pathogens have also come into the focus of science, including herpes viruses. Researchers at Mount Sinai Hospital in New York (USA) recently discovered that the brains of deceased Alzheimer's patients contain a noticeably high number of HHV-6 and -7 viruses. Both interact with genes that increase the risk of Alzheimer's, at least according to computer analysis. The results were published in the journal Neuron in June 2018.

"That is exciting, but it does not mean that there is a causal connection between the viruses and Alzheimer's disease," says Professor Anja Schneider from the German Center for Neurodegenerative Diseases and the University Clinic in Bonn. Almost all adults carry this herpes virus in their body, but not all of them develop Alzheimer's later.

Most of them become infected as infants and small children, thereby developing three-day fever. Defense cells of the immune system successfully fight the intruders, but sometimes do not eliminate them completely.

Viruses and bacteria under suspicion

Antiviral drugs might get rid of them. Schneider doesn't think the time is ripe to test this on people. There is still a lot of experimental work to be done beforehand. "One would have to show, for example, that infected mice develop Alzheimer's disease and that drugs can counteract it," says the expert.

Antiviral therapy is already being tested on volunteers against other widespread herpes viruses. The funds are given to people with mild Alzheimer's disease who harbor herpes simplex viruses, the triggers of cold sores and genital herpes. The study is being conducted at the New York State Psychiatric Institute in the United States and will continue until mid-2022.

But bacteria are also suspected of causing or at least worsening Alzheimer's disease: for example, the pathogen Porphyromonas gingivalis. In people with advanced periodontitis it settles in the deep gum pockets and is jointly responsible for the destruction of the teeth. An international team recently found out: These bacteria and their metabolic product gingipain are also found in the brains of deceased Alzheimer's patients.

Laboratory tests have shown that in infected mice the bacterium gets from the gums to the brain and causes pathological changes such as in Alzheimer's disease. An inhibitor against gingipain slowed the destructive process. The results were published in January in the journal Science Advances. A test on Alzheimer's patients with the inhibitor is scheduled to start this month.

Reinforced by infections

Until then, it remains unproven whether the periodontal germ causes Alzheimer's. It could also be the other way round. Schneider: "The dementia comes first. This makes the blood-brain barrier permeable to pathogens so that they can penetrate the brain." They would only aggravate the pathological process that began many years earlier.

After all, there would then be another argument in favor of the consistent treatment of periodontitis and good oral hygiene. Both are neglected in the care of people with dementia. Studies over the past few years have shown this again and again.