There is marked cortical atrophy in Alzheimer's disease, associated with loss of gyri and sulci in the temporal lobe and parietal lobe, and parts of the frontal cortex and cingulate gyrus. Credit: Doctor Jana/Creative Commons

One of the hallmarks of Alzheimer’s disease is the buildup of the protein amyloid-beta in the brain. Several years ago neurobiologist Rob Moir began wondering about the function of amyloid-beta. Surely it couldn’t just be junk, gumming up the brain? His studies on this protein may be overturning some 30 years of assumptions about what causes Alzheimer’s.

Moir first began wondering about amyloid-beta over Friday night drinks at a bar. 

“Well, it wasn't a bar so much as it was that every Friday we have an attitude readjustment hour at the department and I did indeed take a couple of Coronas,” Moir jokes.

As it turns out, amyloid-beta has antimicrobial properties. Moir and neurologist Rudy Tanzi discovered this in a study several years ago. And now, reporting in Science Translational Medicine, they write that the protein acts as a foot-soldier against fungal and bacterial infection in vitro, and in the brains of nematodes and mice. Within just 48 hours of infection, they saw clumps of amyloid appear in the hippocampi of mice—and trapped in the center of each glob, the invading microbe.

What does this mean for Alzheimer’s? It means, as Moir explains, when someone is infected with a bacteria, fungus or virus, amyloid-beta goes to work making a plaque to clump up and work at a protectant. 

“It's these clumps that are also toxic to nerve cells,” Moir says. “These clumps…bind to the microbe and actually prevent it from binding to a cell like a neuron. So first it prevents the adhesion and then it actually — we say it agglutinates — that means it clumps up the bacteria and the viruses into a big ball … so it can't cause any harm, and eventually kills it. So it's a classic mechanism by which anti-microbial peptides throughout the body do their work to protect us. Except this time it's in the brain and it results in a plaque.”

The plaques, of course, are what cause Alzheimer’s. 

“These plaques are sufficient to trigger the rest of the disease,” Harvard Medical School professor of neurology Rudy Tanzi says. “They trigger these things called tangles, they kill the nerve cells from inside, and they trigger inflammation. So that's the match that lights the fire. In this case it's meant to protect you, but in the end it turns against you.”

Tanzi and Moir aren’t sure which specific infections or bacteria might start the process that eventually results in Alzheimer’s. One of the most closely linked pathogens is the herpes virus, but other candidates include Lymes Disease, candida, or spirochaetes. 

“All of these things could be triggering the same inflammatory response mediated by amyloid-beta that leads eventually to neurodegeneration,” Moir says.

Moir and Tanzi are also unsure why these small, nearly ubiquitous pathogens don’t eventually lead to Alzheimer’s in everyone. Genetics or other risk factors could have something to do with it. Tanzi wonders if lifestyle isn’t part of the issue. 

“After 40, we all have plaques and those plaques start to cause the tangles and inflammation,” Tanzi says. “It's just a matter then of your genetics and your lifestyle. Lifestyle and genetics combine to determine your response to all of this. How do you respond to the plaques and when do you finally succumb to dementia?”

Moir and Tanzi are hoping to expand on their research, and remain hopeful their findings may help develop a treatment for Alzheimer’s. 

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