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Cancer and Alzheimer’s are two of the most dreaded diseases, but they don’t seem to strike the same person too often. In a dark twist of fate, researchers say there could be a good reason for that.

After a 15-year investigative odyssey, a study published in Cell has finally found the molecular messenger behind this mystery. It turns out that peripheral cancers (tumors in the lungs, prostate, or colon) pump out a protein that travels to the brain, recruits the immune system, and systematically dismantles the toxic plaques of Alzheimer’s.

Destroying Plaques

A 2020 meta-analysis (study of studies) of 9.6 million people found that cancer survivors have an 11% decreased incidence of Alzheimer’s. It’s not huge, but it’s enough to suggest something’s up.

Ever since, a research team led by neurologist Youming Lu at Huazhong University of Science and Technology tried to see why this is happening.

We still don’t know exactly what triggers Alzheimer’s, but we do know that a protein called “amyloid beta” plays a key role in the disease. In a healthy brain, these proteins are cleared out regularly. However, in an Alzheimer’s brain, they clump together into “plaques”. These plaques block communication between neurons, eventually killing the cells.

They conducted a mouse study, transplanting human lung, prostate, and colon tumors into mice bred to develop Alzheimer’s. They noticed that the cancer-bearing mice didn’t develop the expected brain plaques. But why?

Protein Wars

The team narrowed the cause down to a protein Cyst-C. When a tumor grows, it leaks this protein into the blood. In the mice, Cyst-C traveled to the brain and found its way inside. Once there, it docked onto a receptor on the microglia called TREM2.

Microglia are the brain’s resident immune cells, the “janitors” of the brain. These cells have been shown to be able to clear out Alzheimer’s plaques, but they don’t always do so. However, when the Cyst-C reaches the microglia, it turbocharges them. They start aggressively devouring the amyloid plaques. And, intriguingly, they don’t just stop new ones from forming, they also break down the ones that are already there.

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It’s a spectacular mechanism — but there’s a catch.

The brain is the most protected organ in the body, wrapped in a tight mesh of cells that prevents almost everything from leaking into the gray matter. That’s part of the reason why it’s so hard to treat brain conditions, because it’s hard to get treatments past this barrier. Dr. Donald Weaver, a top neurologist in Toronto, compared Cyst-C to “trying to drive a bus across the blood-brain barrier.” It’s a large molecule. It shouldn’t be able to get in.

However, Dr. Lu’s research points to a tragic irony. In the early stages of Alzheimer’s, the blood-brain barrier actually starts to “leak”. It could be exactly this early damage caused by early Alzheimer’s that allows the cancer protein to enter and, surprisingly, save the brain.

Can We Use This?

Of course, this doesn’t make cancer a good thing. Rather, it’s distinctly ironic. But this pathway is intriguing, and researchers suspect that we could use these mechanisms and hijack them for good; turbocharge the microglia without the cancer.

Currently, most Alzheimer’s drugs are “inhibitors” — they try to stop something from happening. But activating a protein like TREM2 is significantly harder. This study provides a natural blueprint for an “activator” drug.

The hunt is now on to turn this “tumor signal” into a shelf-stable, safe, and effective injection. It’s a long road, but for the first time, we have a map that explains why the “medical ghost story” could have been true all along.

The study was published in Cell.