As the immune system ages, it enters a state of chronic, low-grade inflammation called ‘inflammaging’.
Training the immune system
So a vaccine that stimulates the immune system would seem an unlikely treatment for a disease driven by brain inflammation. But a new study in Communications Medicine suggests the century-old tuberculosis vaccine Bacillus Calmette-Guérin (BCG) does the opposite: rather than boosting immunity, it retrains innate immune cells within the ageing brain. The study is based on trained immunity, a phenomenon in which certain vaccines give innate immune cells a long-lasting memory, making them more effective against unrelated threats. Unlike antibodies, which recognise specific germs, trained immunity makes the innate immune system respond more effectively to many different threats. Clinicians have also long observed that bladder cancer patients treated with BCG have a lower incidence of dementia. But even with so few cells, the team found that monocytes — the predominant immune cells in cerebrospinal fluid in the study — switched on genes linked to a faster, more alert immune response, mirroring similar changes in the bloodstream. Whether this change in the way immune cells respond actually helps clear amyloid plaques from the brain is a separate question — and here the data suggest a race against time. The study also lacked a placebo group, so it’s impossible to rule out other explanations for the changes observed. Cognitive scores barely moved either way — unsurprising, Dr. Dr. Basak cautioned that any conclusions about the vaccine’s real-world relevance to disease will have to wait for such a trial.
“From a 10-ml blood draw, you get about 10 million immune cells. During a lumbar puncture, you get about 10,000,” said Mahesh Chandra Kodali, a neuroscientist and study co-author at Massachusetts General Hospital.
Kodali said, since “dementia itself occurs over a period of several years,” which is too long for a one-year study to capture. However, he also said the study points to the patterns of gene activity inside the brain’s own immune cells to be a promising new target for future therapies, potentially reaching beyond Alzheimer’s to other neurodegenerative diseases driven by inflammation.
Key Questions
Modern anti-amyloid drugs are expensive, Dr. That’s part of why the Banner Alzheimer’s Institute has submitted a roughly $200-million grant application to fund a large, randomised trial testing BCG as an Alzheimer’s preventive, he said.
Kodali said, whereas BCG is cheap and has decades of safety data behind it.
