For decades, the idea that a bacterium or virus could help cause Alzheimer's was dismissed as marginal theory. But not so much anymore. On Wednesday, a team of researchers from Harvard Medical School in the journal Neuron reported on the latest evidence suggesting that herpes viruses can trigger the cascade of events leading to Alzheimer's disease, a deadly form of dementia, of which at least 5 Millions of Americans Are Affected  The researchers looked at how neurons in mice responded to the presence of herpes simplex 1 (HSV-1), the virus that causes cold sores. In a separate experiment with a 3D model of the human brain that was cultured in a dish, they also studied human herpesvirus 6 (HHV-6), the germ responsible for the development of the skin disease Roseola. These viruses are usually caught early in life and remain asleep somewhere in the body, but as we get older, they almost always go to the brain.
Some of the mice that were used in the experiment were genetically bred to have neurons that could create the human version of amyloid beta (or amyloid-β). Amyloid-β is a protein that is normally produced in the brain. But in Alzheimer's patients, they clump together to form the plaques thought by many experts to slowly destroy the brain. Many scientists have long believed that amyloid-β is essentially a waste product with no meaningful purpose. But the researchers had previously shown that amyloid-β could indeed serve as the first line of defense against fungal and bacterial infections.
In the current study, both viruses appeared to elicit an identical response. The brains of the mice virtually grew "overnight" new deposits of amyloid β plaques, according to senior author Rudy Tanzi, a geneticist specializing in the brain of the Massachusetts General Hospital and Harvard Medical School. And the mice bred with these human-like neurons were better at warding off a brain infection than mice without them. The same effects were also observed in the Petri dish.
"Sowing amyloid causes deposition of plaque," Tanzi said, "and herpes viruses and other microbes can quickly seed amyloid β."
The study is the second in recent weeks to support the role of viruses in Alzheimer's disease. This first study, also published in Neuron and led by researchers from the Icahn School of Medicine at Mount Sinai, found evidence that certain herpes viruses are more commonly found in the brains of people who have died from Alzheimer's disease; it also suggests that genes belonging to these viruses interact directly with human genes that increase the risk of the disease.
Timing is no coincidence, Tanzi said. His team has corresponded with the Mount Sinai team for years, and they had originally planned to release their results at the same time (both will be published in the same Print July issue of the magazine). It was the Mount Sinai team, Tanzi said, that the Harvard team investigated HHV-6 and HSV-1 in their experiments, as this was the virus they used to get to work on their work.
While Tanzi and his team acknowledge the long-ignored work of other researchers supporting the so-called viral hypothesis of Alzheimer's disease, he said their research is taking things in a slightly different direction. It's an attempt to reconcile different theories about what causes Alzheimer's.
Proponents of virus theory have often speculated that germs such as HSV-1 – the most commonly accused culprit – cause the brain to become out of control due to inflammation. Amyloid-β is just a bystander. But in Tanzi's version, amyloid-β is still the key to the disease. Neurons use the protein to either kill viral or bacterial particles in a "nano-net" or capture them safely, as Tanzi puts it. In Alzheimer's disease, however, the process gets out of hand and leads to an uncontrolled build-up of plaques. From there, according to Tanzi's work, the plaques trigger the formation of tangles – lumps of another brain protein called tau, which is seen in the later stages of Alzheimer's disease – that together trigger a chronic inflammation. All these moving parts align themselves with the brain and ultimately cause death.
In this scenario, it is not the germ that is responsible but the immune system. "The microbes are the prequel to the amyloid hypothesis," Tanzi said.
Viruses are just one of the things that could trigger Alzheimer's, he said. The same type of seeding could happen in people whose genes cause them to produce too much amyloid-β in the absence of infection. And genetics could help explain why only some people cause infections, that the brain begins to produce amyloid-β en masse. "Only the virus is not enough," said Tanzi.
But with the widespread failure of Alzheimer's treatments aimed at amyloid-β production, the viral compound provides a new, clear direction for future clinical trials: preventive antimicrobial drugs or vaccines that can prevent them Germs will ever reach the brain in the first place. Some recent observational studies (ie uncontrolled studies) have already indicated that these drugs may reduce the risk of dementia.
These types of definitive studies are probably still a while away, but there is certainly a change in the headwinds.
"I think we've gotten beyond the point where this idea is being ridiculed, but some could still strongly oppose it," Tanzi said, referring to the 19th-century maxim of German philosopher Arthur Schopenhauer about the three stages of truth ridicule, then fierce resistance and finally acceptance for granted).
The buck will probably not stop with herpes either. Tanzi and his team are already researching how the bacteria living in the brain can contribute to Alzheimer's. Tanzi is also part of a research project that seeks to map the living microbial universe or microbiome of the brain and how it might affect our mental and physical health.