Animal experiments have confirmed that aged immune cells in the blood cause memory and cognitive decline. Getty Images Bank
A new study has found that the cause of age-related decline in memory and cognitive function lies in immune cells within the blood. Animal experiments have confirmed that simply inhibiting these immune cells in the blood could prevent memory and cognitive decline. This is gaining attention as a new clue for treating dementia, including Alzheimer’s disease.
A team led by Professor Saul Villeda at the University of California, San Francisco (UCSF) published findings in the international journal *Immunity* on the 14th (local time) showing that aged ‘CD8+ T cells’ circulating in the blood and the substances they secrete cause memory and cognitive decline. CD8+ T cells are a type of immune cell that attacks and eliminates virus-infected cells or cancer cells.
The research team used a technique called ‘parabiosis,’ where the blood vessels of old and young mice are surgically connected to share blood, to see if the properties of old mice’s CD8+ T cells would change when exposed to a young or old blood environment.
The results showed that the characteristics of aged CD8+ T cells did not change even when placed in a young blood environment. When aged CD8+ T cells were injected into young mice, the expression of genes related to memory and cognitive function decreased in the hippocampus, the brain region responsible for memory and learning. Their performance on tasks like maze navigation and object recognition also declined.
Conversely, when these cells were reduced in old mice using antibodies, their performance on cognitive tasks improved.
The team identified the enzyme ‘Granzyme K (GZMK),’ secreted by CD8+ T cells, as the key culprit. GZMK is a protein-degrading enzyme originally used by immune cells to eliminate pathogens. When excessively secreted by aged CD8+ T cells, it causes inflammation. Inhibiting GZMK with a drug improved the maze performance of old mice.
Professor Villeda told *Nature*, “GZMK could be a promising target for treating dementia, including Alzheimer’s disease,” adding, “We have already secured a candidate therapeutic substance.” Further research is needed to determine if the animal experiment results apply to humans. It also remains unknown why aged CD8+ T cells secrete more GZMK and through what pathway this enzyme affects brain function.
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doi.org/10.1016/j.immuni.2026.04.014
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