People with cancer often face treatments and body-wide changes like inflammation, stress, and vascular damage—factors also linked to a higher risk of Alzheimer’s disease (AD). Surprisingly, large studies around the world consistently show the opposite: people with a history of cancer are less likely to be diagnosed with AD. This surprising finding raises an important question: how might cancer protect the brain against Alzheimer’s? One promising explanation involves tiny particles called extracellular vesicles (EVs). Tumors release huge numbers of EVs into the blood, and these vesicles can cross into the brain. Inside them are molecules called microRNAs (miRNAs), which act like genetic “switches” that control how cells function. We believe cancer-derived EV miRNAs might change brain cells to clear harmful proteins, reduce damage, and ultimately guard against Alzheimer’s. Our early studies support this idea. We found that people with both cancer and Alzheimer’s had brain cells better equipped to remove amyloid plaques. In mice, introducing cancer cells or cancer-derived EVs reduced plaque buildup and activated protective brain responses. In this project, we will (1) study how cancer-derived EV miRNAs reprogram brain cells in mouse models of AD, (2) analyze large human cancer and AD datasets to uncover shared miRNA networks, and (3) test top candidate miRNAs by delivering them directly to AD mouse models. This work could explain why cancer patients are less likely to develop AD and lead to new treatments that harness these protective pathways for Alzheimer’s patients.
