Recent research has shown that targeting microglia in a mouse model of Alzheimer’s disease to suppress p16 expression can effectively reduce amyloid-β plaques. This approach aims to address a maladaptive response from microglia, the innate immune cells responsible for clearing debris from the brain. P16, a marker of cellular senescence, is found in both senescent and pro-inflammatory microglia. Senolytic therapies can help eliminate senescent cells, while regulating non-senescent, activated microglia requires a different strategy. Additionally, aging microglia have reduced ability to clear amyloid, suggesting that regulating their cell cycle could enhance amyloid clearance. By downregulating p16ink4a in microglia, researchers have successfully reduced amyloid plaque formation, reversed learning and memory deficits, and proposed a promising strategy for treating Alzheimer’s disease. For more information, you can access the study at https://doi.org/10.1186/s13024-024-00715-x.