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Could cancer hold answers to the treatment of Alzheimer’s Disease? A recent paper suggests that a protein released by cancer cells may lead to degradation of characteristic protein aggregates in Alzheimer’s Disease.

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Cancer has long been one of the most devastating diseases worldwide, accounting for nearly 10 million deaths in 2022 alone. But what if it also held answers to the treatment of yet another devastating disease? For many years, scientists have noticed that people rarely develop both cancer and Alzheimer’s disease (AD). In fact, there is data to suggest that a cancer diagnosis reduces the risk of an AD diagnosis by around 11%. Could this mean that cancer might somehow protect patients from AD? This is a difficult question to answer, as there are many outside factors that may influence this statistic. For instance, cancer patients may not live long enough to develop AD, or cognitive effects of cancer treatment may make an AD diagnosis less likely. Nonetheless, a recent paper has sought to decipher the relationship between the two diseases.

To do this, the researchers first set out to model both cancer and AD in mice. They accomplished this by injecting cancer cells into AD model mice, which are engineered to recapitulate hallmarks of AD. For instance, AD is characterized by the accumulation of a protein called beta-amyloid in the brain. In AD, this protein forms clumps, known as plaques, that build up between neurons. This can lead to many cognitive defects such as memory loss and confusion. Left untreated, the AD model mice used in this paper exhibit similar symptoms. They not only develop amyloid-beta plaques, but also exhibit the cognitive defects associated with AD. However, when these mice were given cancer, through injection of cancer cells, formation of amyloid-beta plaques was reduced. This same effect was seen when AD model mice were injected with proteins that are released by cancer cells (cancer cell secretory proteins/CSPs) rather than the cancer cells themselves. In some tests, injection of CSPs also improved memory in the AD mice.

This led the researchers to ask which of the CSPs were leading to these effects. Through a number of screens, they landed on one protein called cystatin-C (Cyst-C). They found that Cyst-C was able to cross the blood-brain barrier and interact with aggregates of amyloid-beta. Additionally, Cyst-C was able to activate another protein called TREM-2 in a type of immune cell called microglia. This activation of TREM-2 then allowed microglia to engulf and subsequently degrade amyloid beta plaques.

These findings have the potential to lead to new and exciting strategies for the treatment of AD. In fact, even before this paper was published, scientists had already been trying to develop drugs that could activate TREM-2 for the treatment of AD. Therefore, the discovery that Cyst-C activates TREM-2 is very useful to the field. Of course, it is important to note that all of this research was done in mice. These results should be confirmed in humans before basing any treatments around them. Nonetheless, this paper provides interesting insight into the relationship between cancer and AD and demonstrates a potential mechanism by which the former may protect from the latter.

Edited by Ethan Honeycutt & Jayati Sharma