Old TB Vaccine Trains Brain Cells to Fight Alzheimer's

The aging immune system's chronic inflammation, known as 'inflammaging,' particularly damages the brain in Alzheimer's disease. Immune cells that typically clear toxic amyloid-beta become dysfunctional, fueling neuroinflammation. A new study suggests the tuberculosis vaccine, Bacillus Calmette-Guérin (BCG), may counteract this by retraining innate immune cells.

This phenomenon, termed trained immunity, equips innate immune cells with a long-lasting memory, enhancing their response to various threats. Researchers at Massachusetts General Hospital studied 23 older adults, administering BCG to assess its impact on the central nervous system's immune cells.

Analysis of cerebrospinal fluid revealed that monocytes, a key immune cell type, switched on genes associated with a faster, more alert immune response. This effect was observed even though the cells did not show a stronger reaction to BCG itself but to an unrelated bacterial molecule.

While promising, the vaccine's effect on amyloid plaque clearance appears to be a race against time. In participants without established Alzheimer's, amyloid levels decreased in cerebrospinal fluid, indicating potential clearance. However, this effect was not observed in those with established Alzheimer's, possibly due to the overwhelming inflammatory environment.

This suggests BCG might be more effective as a preventive measure than a treatment for advanced Alzheimer's. The study, though small and lacking a placebo group, highlights gene activity patterns in the brain's immune cells as a potential therapeutic target for neurodegenerative diseases.