Alzheimer’s disease (AD) and cancer both represent diseases that classically occur in older individuals. However, these diseases rarely occur in the same individuals. In fact, individuals with AD have a 50% less risk of cancer than those without, and similarly, those with cancer have a 35% lower risk of developing AD than those without a history of cancer. While this phenomenon has long been recognized by doctors and scientists, experts have speculated that one disease could only speculate that one disease protects bearers from the other.
A paper recently published in the journal Cell provides new evidence supporting a protective effect of cancer against AD. The pre-clinical study identifies a protein, TREM2, which acts in the brain, actively breaking down plaques that predispose an individual to AD and other neurological conditions.
Plaques form when beta-amyloid proteins degrade and clump together between neurons in the brain. The accumulation of plaques impairs cell communication, causing cell damage and inflammation that can lead to memory loss.
The researchers implanted mouse lung, prostate, and colon cancer into mouse models of AD. The tumor-bearing mice did not develop amyloid plaques, despite being predisposed to AD.
Further investigation showed that tumor-bearing mice secreted cystatin-c, a protein that binds to the plaques in the brain characteristic of AD. The engagement between cystatin-c and plaques activates a cell surface protein known as “triggering receptor expressed on myeloid cells 2” (TREM2). Normally located on immune cells, including microglia, TREM2, which is present in the central nervous system, plays a critical role in regulating inflammation. The study shows that TREM2 activation led to the degradation of pre-existing amyloid plaques.
The current study included only pre-clinical analysis. However, confirmation that similar signaling pathways operate in humans could provide researchers with important targets for developing drugs to treat, control, or even prevent AD.
Sources: Science Transl Med, Cell Metabol, Neurol, Cell