Infectious Theory of Alzheimer Disease Draws Fresh Interest

Bret S. Stetka, MD

Disclosures

November 14, 2018

The hallmark pathology of Alzheimer's is accumulation of a protein called amyloid in the brain. Many researchers have assumed that these aggregates, or plaques, are simply a byproduct of some other process at the core of the disease. Other scientists posit that the protein itself contributes to the condition in some way.

The theory that amyloid is the root cause of Alzheimer's is losing steam. But the protein may still contribute to the disease, even if it winds up being deemed infectious.

Work by Harvard neuroscientist Rudolph Tanzi[6] suggests that it might be a bit of both. Along with colleague Robert Moir, Tanzi has shown that amyloid is lethal to viruses and bacteria in the test tube and also in mice. He now believes that the protein is part of our ancient immune system that, like antibodies, ramps up its activity to help fend off unwanted bugs.

So does that mean that the microbe is the cause of Alzheimer's, and amyloid a harmless reaction to it? According to Tanzi, it's not that simple.

Tanzi believes that in many cases of Alzheimer's, microbes are probably the initial seed that sets off a toxic tumble of molecular dominoes. Early in the disease process, amyloid protein builds up to fight infection, yet too much of the protein begins to impair function of neurons in the brain. The excess amyloid then causes another protein, tau, to form tangles, which further harm brain cells.

But as Tanzi explains, the ultimate neurologic insult in Alzheimer's is the body's reaction to this neurotoxic mess. All of the excess protein revs up the immune system, causing inflammation—and it's this inflammation that does the most damage to the Alzheimer's-afflicted brain.

What does this say about the future of treatment? Possibly a lot. Tanzi envisions a day when people are screened at, say, 50 years old. "If their brains are riddled with too much amyloid," he says, "we knock it down a bit with antiviral medications. It's just like how you are prescribed preventive drugs if your cholesterol is too high."

Tanzi feels that microbes are just one possible seed for the complex pathology behind Alzheimer's. Genetics may also play a role, as certain genes produce a type of amyloid more prone to clumping up. He also feels that environmental factors like pollution might contribute.

Dr James Burke, professor of medicine and psychiatry at Duke University's Alzheimer's Disease Research Center, isn't willing to abandon the amyloid theory altogether but agrees that it's time for the field to move on. "There may be many roads to developing Alzheimer's disease, and it would be shortsighted to focus just on amyloid and tau," he says. "A million-dollar prize is attention-getting, but the reward for identifying a treatable target to delay or prevent Alzheimer's disease is invaluable."

Any treatment that disrupts the cascade leading to amyloid, tau, and inflammation could theoretically benefit an at-risk brain. The vast majority of Alzheimer's treatment trials have failed, including many targeting amyloid. But it could be that the patients included were too far along in their disease to reap any therapeutic benefit.

If a microbe is responsible for all or some cases of Alzheimer's, perhaps future treatments or preventive approaches will prevent toxin protein buildup in the first place. Both Tanzi and Norins believe that Alzheimer's vaccines against viruses like herpes might one day become common practice.

In July of this year, in collaboration with Norins, the Infectious Diseases Society of America announced that it plans to offer two $50,000 grants supporting research into a microbial association with Alzheimer's. According to Norins, this is the first acknowledgement by a leading infectious disease group that Alzheimer's may be microbial in nature—or at least that it's worth exploring.

"The important thing is not the amount of money, which is a pittance compared with the $2 billion that NIH spends on amyloid and tau research," says Norins, "but rather the respectability and more mainstream status that the grants confer on investigating the infectious possibility. Remember when we thought ulcers were caused by stress?"

Ulcers, we now know, are caused by a germ.

This article originally appeared on Shots, NPR's health blog.

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