Infectious Theory of Alzheimer Disease Draws Fresh Interest

Bret S. Stetka, MD

Disclosures

November 14, 2018

Dr Leslie Norins is willing to hand over $1 million of his own money to anyone who can clarify something: Is Alzheimer disease, the most common form of dementia worldwide, caused by a germ?

By "germ," he means microbes like bacteria, viruses, fungi, and parasites. In other words, Norins, a physician-turned-publisher, wants to know whether Alzheimer's is infectious.

It's an idea that just a few years ago would have seemed to many an easy way to drain one's research budget on bunk science. Money has poured into Alzheimer's research for years, but until very recently not much of it went toward investigating an infectious cause of dementia.

But this "germ theory" of Alzheimer's, as Norins calls it, has been fermenting in the literature for decades. Even early 20th century Czech physician Oskar Fischer—who, along with his German contemporary Dr Alois Alzheimer, was integral in first describing the condition—noted a possible connection between the newly identified dementia and tuberculosis.

If the germ theory gets traction, even in only a subset of Alzheimer's patients, it could trigger a seismic shift in how doctors understand and treat the disease.

For instance, would we see a day when dementia is prevented with a vaccine or treated with antibiotics and antiviral medications? Norins thinks it's worth looking into.

Norins received his medical degree from Duke in the early 1960s, and after a stint at the Centers for Disease Control and Prevention he fell into a lucrative career in medical publishing. He eventually settled in an admittedly aged community in Naples, Florida, where he took an interest in dementia and began reading up on the condition.

After scouring the medical literature he noticed a pattern.

"It appeared that many of the reported characteristics of Alzheimer disease were compatible with an infectious process," Norins tells NPR. "I thought for sure this must have already been investigated, because millions and millions of dollars have been spent on Alzheimer's research."

But aside from scattered interest through the decades, this wasn't the case.

In 2017, Norins launched Alzheimer's Germ Quest Inc., a public benefit corporation he hopes will drive interest to the germ theory of Alzheimer's, and through which his prize will be distributed. A white paper he penned for the site reads: "From a two-year review of the scientific literature, I believe it's now clear that just one germ—identity not yet specified, and possibly not yet discovered—causes most AD. I'm calling it the 'Alzheimer's Germ.'"

Norins is quick to cite sources and studies supporting his claim, among them a 2010 study published in the Journal of Neurosurgery[1] showing that neurosurgeons die from Alzheimer's at a rate nearly 2.5 times higher than that of the general population.

Another study from that same year, published in the Journal of the American Geriatric Society,[2] found that people whose spouses have dementia are at a 1.6 times greater risk for the condition themselves.

Contagion does come to mind. And Norins isn't alone in his thinking.

In 2016, 32 researchers from universities around the world signed an editorial in the Journal of Alzheimer's Disease[3] calling for "further research on the role of infectious agents in [Alzheimer's] causation." On the basis of much of the same evidence that Norins encountered, the authors concluded that clinical trials with antimicrobial drugs in Alzheimer's are now justified.

An intriguing study published in Neuron[4] in July suggests that viral infection can influence the progression of Alzheimer's. Led by Mount Sinai genetics professor Joel Dudley, the work was intended to compare the genomes of healthy brain tissue with those affected by dementia.

But something kept getting in the way: herpes.

Dudley's team noticed an unexpectedly high level of viral DNA from two human herpes viruses, HHV-6 and HHV-7. The viruses are common and cause a rash called roseola in young children (not the sexually transmitted disease caused by other strains).

Some viruses have the ability to lie dormant in our neurons for decades by incorporating their genomes into our own. The classic example is chickenpox: A childhood viral infection resolves and lurks silently, returning years later as shingles, an excruciating rash. Like it or not, nearly all of us are chimeras with viral DNA speckling our genomes.

But having the herpes viruses alone doesn't spell inevitable brain decline. After all, up to 75% of us may harbor HHV-6.[5]

But Dudley also noticed that herpes appeared to interact with human genes known to increase Alzheimer's risk. Perhaps, he says, there is some toxic combination of genetic and infectious influence that results in the disease—a combination that sparks what some feel is the main contributor to the disease, an overactive immune system.

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