For some time, we've known that it's rare to see people with both cancer and Alzheimer's disease. Now, scientists believe they may have found why, discovering a molecule in cancer cells that clears problem proteins from the brain.
Following 15 years of work, researchers from the University of Toronto have uncovered a specific molecule found in cancerous cells that can break down misfolded proteins in the brain, allowing for them to be cleared out instead of accumulating. In Alzheimer’s disease (AD), the build-up of misfolded amyloid-beta plaques and tau tangles destroys the brain's cells and leads to cognitive decline.
While the discovery was made using a mouse model, it's the closest we've gotten to understanding the strange connection between two of our most devastating diseases. And while it seems counterproductive that one could actually protect us from developing the other, there's mounting evidence this is the case. So much so that scientists have found that some cancer treatments have delivered positive results in slowing cognitive decline.
In this study, the researchers found that not all but some cancers release a protein called cystatin-C (Cyst-C), which travels through the body and helps the brain clear away toxic amyloid clumps – the sticky protein build-up linked to Alzheimer’s disease. Cyst-C binds to these small, harmful amyloid clusters and “switches on” the brain’s immune cells – microglia – to recruit them in helping break down the plaques.
When the researchers disabled the Cyst-C pathway, this seemingly protective effect vanished. It was enough to convince the scientists that the cancer protein–immune interaction is essential for clearing plaques and therefore reducing the risk of developing AD.
"They have a piece of the puzzle," Donald Weaver, a neurologist at the Krembil Research Institute at the University of Toronto in Canada, who was not involved in the study, told Nature. "It’s not the full picture by any stretch of the imagination. But it’s an interesting piece."
While many scientists have believed for some time there's a mysterious relationship between AD and cancer, disease pathology has made it difficult to understand. Though cancer patients, overall, have a reduced incidence of AD, there are many factors at play here – including that individuals might die long before age-related AD would be expected to show up, and "chemo brain" can mirror the early stages of cognitive decline.
Here, the researchers transplanted three types of human tumor – lung, prostate and colon – into mouse models of AD. The mice with cancer remained free of the plaques characteristic of cognitive decline. This tipped the scientists off that there must be some molecule from the cancerous cells that can cross the blood-brain barrier and inflict good, not harm. It took six years to find that it was the protein Cyst-C.
While preliminary, it opens the door to developing drugs that can break down misfolded plaques and even prevent their formation – without having to endure cancer. It also advances the search for existing cancer drugs that might be beneficial for the brain.
"Together, these findings provide significant conceptual advances into cancer neuroscience and establish therapeutic avenues that are distinct from the present amyloid-lowering strategies, aiming at degrading the existing amyloid plaques for precision-targeted AD therapy," the researchers noted.
The research was published in the journal Cell.
Source: University of Toronto via Nature
