A Causal Link Between Alzheimer’s Disease and Cancer

Though they may seem like unrelated diseases, cancer and Alzheimer’s disease are more closely linked than you’d expect. As I’ve discussed previously on the blog, scientists have been aware for nearly 15 years that these two conditions are inversely correlated. In other words, cancer survivors have a lower risk of later developing Alzheimer’s disease, and vice versa.

According to one meta-analysis, Alzheimer’s patients have a 42% reduced risk of developing any kind of cancer in their lifetime, while cancer survivors have a 37% reduced risk of Alzheimer’s disease. Notably, this correlation is not caused by decreased life expectancy or different lifestyle choices, as the analysis took these factors into account in their calculations.

While those numbers look pretty convincing, we must be careful when interpreting the results of observational studies. A scientist’s favorite mantra is “correlation does not imply causation.” In other words, based on these studies alone, we have no way to know whether cancer directly protects against Alzheimer’s disease, Alzheimer’s directly protects against cancer, or some unknown third factor is linking the two diseases indirectly. We can’t determine a causal relationship from observation alone.

However, a recent study published in Scientific Reports attempts to address this dilemma. Researchers from the University of Cambridge used a technique called Mendelian randomization to determine causality. Essentially, this involves searching for genetic variants that are known to increase the risk of cancer, and then determining whether those same variants also decrease the risk of Alzheimer’s. By probing at the genetic level, this technique allows researchers to directly determine whether cancer is protective against Alzheimer’s.

Using data from public repositories, the authors determined that several genetic variants involved in cancer risk are protective against Alzheimer’s. Overall, a 10-fold (1000%) higher genetic risk for developing cancer results in a 2.5% reduced risk of Alzheimer’s. That may seem like a small reduction, but keep in mind that this represents only the genetic component of risk. Since both cancer and Alzheimer’s are complex diseases and heavily influenced by non-genetic factors, these numbers encapsulate only a small portion of an individual’s overall risk.

Importantly, this study is the first to show a causative link (rather than merely a correlation) between Alzheimer’s disease and cancer. The study’s lead author, Sahba Seddighi, stated, “Our results offer novel possibilities for targetable pathways in Alzheimer’s disease—which remains without a cure, despite a rapidly growing aging population—and call for a deeper understanding of the underlying mechanisms behind this relationship.”

So what does this link really mean? In a way, it makes some intuitive sense: cancer is the result of uncontrolled cell growth and proliferation, while Alzheimer’s is associated with cell death and degeneration. But what genetic interactions and cell signaling pathways are involved remains unknown.

In the meantime, by shedding new light on the genetic underpinnings of Alzheimer’s, the study brings a new insight to the field, which will hopefully bring scientists one step closer to finding a cure.

 

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