TB vaccine offers clue to retrain immune system against Alzheimer’s

Alzheimer's disease is caused by brain inflammation, which is exacerbated by dysfunctional immune cells that clear toxic proteins. Vaccines usually boost immunity, but a new study on the century-old tuberculosis vaccine, Bacillus Calmette-Guérin (BCG), suggests it actually retrains the immune system within the aging brain. This trained immunity allows innate immune cells to respond more effectively to various threats.

The study, conducted at Massachusetts General Hospital, enrolled 23 older adults, half with and half without Alzheimer's biomarkers, who received two BCG doses a month apart. Blood and cerebrospinal fluid samples were collected over the year following the vaccination. The researchers found that monocytes in cerebrospinal fluid switched on genes linked to a faster, more alert immune response, similar to changes in the blood.

When exposed to BCG again, the cells did not respond more strongly, but they did respond more strongly to an unrelated bacterial molecule, suggesting the vaccine put cells on general alert. In participants without established Alzheimer's, amyloid levels fell in cerebrospinal fluid and rose in the blood, indicating that retrained immune cells help move amyloid out of the brain.

However, this effect was not observed in participants with established Alzheimer's. The study also noted that a damaged blood-brain barrier or dense amyloid plaques could impede amyloid clearance, even if immune cells were retrained. While the vaccine triggered a sustained rise in inflammatory signaling proteins in blood plasma, especially in Alzheimer's patients, the cerebrospinal fluid changed into a calming, regulatory state in everyone, indicating a shift away from neuroinflammation.

The study's limitations, including its small sample size and lack of a placebo group, prevent strong conclusions about its therapeutic or preventive potential for Alzheimer's. However, the study's findings suggest that BCG's effects rely on slow chemical modifications that may take longer than a year to fully show up. This aligns with broader patterns in BCG research, and a larger, randomized trial is planned to test the vaccine as a preventive and therapeutic measure for Alzheimer's.