Lab-grown immune cells improved memory and reduced brain damage in ageing and Alzheimer’s mice, suggesting a possible new way to treat the condition.
The engineered cells, developed from human stem cells, appeared to reverse some effects of ageing and brain damage caused by disease in mouse models.
These immune cells, known as mononuclear phagocytes, normally circulate through the body clearing cellular waste.
As people age, they become less efficient, removing less debris and triggering inflammation – both key features of age-related diseases such as Alzheimer’s.
Researchers from Cedars-Sinai Medical Center in the US created replacement mononuclear phagocytes using human induced pluripotent stem cells – starter cells that can be reprogrammed into many different cell types.
“Previous studies have shown that transfusions of blood or plasma from young mice improved cognitive decline in older mice, but that is difficult to translate into a therapy,” said biomedical scientist Clive Svendsen.
“Our approach was to use young immune cells that we can manufacture in the lab – and we found that they have beneficial effects in both ageing mice and mouse models of Alzheimer’s disease.”
Treated mice performed better on memory tests and developed healthier microglia – immune cells in the brain that clear waste but become depleted with age and Alzheimer’s.
The treatment also increased the number of mossy cells, which help the hippocampus – the brain’s memory control centre – function properly. These cells typically decline with ageing and Alzheimer’s.
“The numbers of mossy cells decline with ageing and Alzheimer’s disease,” said neuroscientist and lead author Alexandra Moser.
“We did not see that decline in mice receiving young mononuclear phagocytes, and we believe this may be responsible for some of the memory improvements that we observed.”
The researchers had hypothesised that mononuclear phagocytes might explain why blood plasma and bone marrow transfusions appear to have rejuvenating effects, and their findings supported this idea.
However, the engineered immune cells injected into the mice did not appear to reach the animals’ brains directly.
The team believes the effects were instead caused by anti-ageing proteins or extracellular vesicles – microscopic parcels that carry chemical signals between cells – released by the younger, fitter immune cells.
These may have travelled to the brain, reducing inflammation and boosting immunity.
Most benefits were seen in older mice rather than those genetically modified to show Alzheimer’s symptoms.
Significant Alzheimer’s-related brain damage, including amyloid-beta protein buildup – toxic protein clumps characteristic of the disease – was not repaired.
Researchers caution that the same effects may not occur in human brains, though the approach shows promise.
Using immune cells derived from a patient’s own stem cells could help overcome some of the limitations of blood plasma and bone marrow transfusions.
“These findings show that short-term treatment improved cognition and brain health, making them a promising candidate to address age- and Alzheimer’s disease-related cognitive decline,” said Cedars-Sinai neuropathologist Jeffrey Golden, who was not directly involved in the study.
The researchers suggest that future work could examine whether longer treatment durations or different dosing strategies might strengthen the benefits, particularly in Alzheimer’s-specific brain damage.