Remodelling of immune system by TB vaccine may explain its link with lower Alzheimer’s risk: Study

The remodelling of the human brain’s immune environment by the tuberculosis vaccine BCG could offer a potential biological explanation for previously observed links between the vaccine and lower Alzheimer’s disease risk, according to a study.

Delivered through the skin, the Bacillus Calmette-Guérin (BCG) vaccine is administered to infants and young children to protect against the bacterial infectious disease marked by severe cough and chest pain, among other symptoms.

Findings published in the journal Communications Medicine show that BCG promoted an increased responsiveness in immune cells surrounding the brain and modified Alzheimer’s-related biomarkers in healthy, older adults with no physical changes due to the neurodegenerative condition.

“BCG is much more than a vaccine against tuberculosis. It is one of the best-studied examples of ‘trained immunity’, a process in which innate immune cells undergo long-lasting functional reprogramming after exposure to certain microbial stimuli,” a co-first author, Mahesh Chandra Kodali, senior research fellow at the Harvard Medical School and Massachusetts General Hospital, US, said.

“This immune reprogramming can persist for months or even years and influence responses well beyond protection against tuberculosis,” Kodali told PTI.

Prior research involving preclinical models, retrospective studies, and randomised clinical trials has suggested that BCG can also reduce Alzheimer’s risk, amyloid pathology — clumping of amyloid proteins in the brain is considered a hallmark of Alzheimer’s disease — and modulate neuroinflammation, researchers said.

“These observations led us to ask whether BCG could influence biological processes relevant to Alzheimer’s disease in humans,” Kodali said.

Twenty three adults aged 55 years and older were recruited, of whom 11 adults showed Alzheimer’s pathology — physical changes associated with the disease — and 12 adults without. Cerebrospinal fluid and peripheral blood samples were obtained from participants at regular intervals for a year after vaccination.

“We found that BCG changed how immune cells behaved, including in the fluid surrounding the brain and spinal cord, and altered markers linked to Alzheimer’s disease,” the authors wrote.

“These findings suggest that boosting the immune system in specific ways may help maintain brain health during aging, but larger studies are needed to understand whether this could prevent or treat disease,” they said.

BCG also shifted levels of amyloid-beta in the cerebrospinal fluid and bloodstream.

Among the healthy participants without Alzheimer’s disease pathology, amyloid levels declined significantly in brain and spinal fluid, while increasing in blood samples over 12 months.

The shift in balance was not seen in the participants showing Alzheimer’s pathology, indicating no measurable effect in the group, and suggesting that the timing of administering BCG might affect early disease dynamics and protein clearance from the central nervous system.

“Our study suggests that (a) controlled mycobacterial immune stimulation can influence biological pathways related to Alzheimer’s disease,” Kodali said.

Randomised clinical trials with larger cohorts would be needed and longitudinal studies would need to distinguish between a prior BCG vaccination, latent or active tuberculosis infection, and Alzheimer’s disease progression, the author added.