Why a scorned theory of Alzheimer’s is hot again

Could a virus or a bacterium give you Alzheimer’s disease? The idea may sound far-fetched, but the hypothesis that microbes may be the missing link in explaining Alzheimer’s is now gaining traction, after being dismissed for decades.

Today we know that trillions of microbes call the human body home - indeed, the majority of the cells in our bodies are non-human. We also know that infections don’t need to produce immediate sickness—microbes can remain hidden in our bodies in a dormant state for years. The chicken pox virus, for instance, can cause chicken pox during childhood but then stay dormant and re-attack decades later to cause painful shingles. Stress, low immunity, lack of sleep and other unknown factors can trigger such reactivation.

Many chronic diseases, not normally thought of as infectious, are now being looked at in a new light, as possibly caused by microbes. And we also know that not all diseases caused by microbes are contagious. The prevailing orthodoxy that stress caused stomach ulcers was dis-proven when doctors noticed that antibiotics prevented their recurrence; now, we know that a bacterium called Helicobacter pylori causes ulcers. Today we also know that almost all cases of cervical cancer are due to the human papilloma virus, and vaccines against the virus have been developed to help lower incidence of the cancer.

So what about examples of bugs causing cognitive disorders? Even though humans have a barrier between our blood vessels and our brain, this barrier becomes leaky as we age.

Microbes can also enter the brain by sneaking through when our immune systems are weak, or even hijacking immune cells to catch a ride in. And there are many illustrations of how this can cause dementia or other behavioral changes. Fatal dementias like scrapie and mad cow disease in animals are known to be caused by infectious agents and some may even infect humans—eating infected beef can cause a type of dementia in humans. Untreated syphilis has long been known to cause dementia – Al Capone is rumored to have been one of its victims.

And in the early days of AIDS, before effective antiretroviral therapies, about half of all infected people develop HIV-associated dementia. In a case that affects even more people, the parasite Toxoplasmosis gondii, carried by cats, can cause slower thinking, distracted driving, and an altered personality in people. Some 2 billion people around the globe are thought to be infected by toxoplasmosis.

So could Alzheimer’s be triggered by microbes? Scientists know that there’s a link between Alzheimer’s and clumps of proteins—dubbed beta-amyloid plaques and tau tangles—in the brain. And those clumps of proteins spread within the brain much like an infection does – though no one knows what initiates them in the first place. One possibility: herpes simplex virus 1 (HSV1), which is carried by some 80% of Americans by age 60 and causes cold sores.

The virus, which is known to be able to replicate in the brain and trigger inflammation, destroys connections between brain cells and attacks the brain’s memory centers to cause an acute form of memory loss. Indeed, one of us (Ruth Itzhaki) was the first to discover its presence in the Alzheimer’s brain and the link between infection and an Alzheimer’s risk gene called Apolipoprotein E4.

But other microbes – such as spirochetes, fungi and bacteria - could have similar impacts. Recently, researchers at Brigham Young University found that people who had been exposed to more infections, and had a higher number of antibodies in their blood for agents including the toxoplasmosis parasite and the hepatitis and herpes viruses, scored worse on tests of memory and cognition. While the effect was small, this study suggests that the cumulative load from multiple infections may contribute to cognitive problems, with a leading culprit being the HSV1.

There are still many unanswered questions. One way to prove the infectious theory of Alzheimer’s would be to infect an animal with brain tissue from an Alzheimer’s patient’s brain and see if the animal shows cognitive changes. Scientists at Harvard recently demonstrated that injecting salmonella (a type of bacterium) into young mice lead to a rapid (overnight) seeding of plaques in the brain’s memory center – suggesting the plaque protein may play an antimicrobial role.

Of course the ultimate way to prove this hypothesis would be to show that treating patients with a vaccine or anti-microbials helps slow down or even stop, progression of the disease. For now, we still don’t know for sure whether microbes could be linked to Alzheimer’s. But considering it has been more than a decade since any new dementia treatments were approved, and many avenues of research are leading to dead ends, it seems an idea worth pursuing.