ArticleCommunications medicine2026
Bacillus Calmette-Guérin (BCG) immunotherapy reprograms CNS immunity and alters Alzheimer's biomarkers: results from two open-label clinical trials.
Article in Communications medicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 2 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Effects of Bacillus Calmette-Guérin (BCG) Immunization on Cerebrospinal Fluid (CSF) and Blood-Based Biomarkers in Older Adults: A Pilot
An Open-label Trial to Evaluate the Effects of BCG Immunization on Biomarkers of Inflammation/Immune Response and Alzheimer's Disease in Adults With Mild Cognitive Impairment and Mild-to-Moderate Dementia Due to Alzheimer's Disease
Who cites it
2 citing papers in PubMed.
- Review
- Role of Exosomes During Mycobacterium Tuberculosis Infection: A Double-Edged Sword.Biomedicines · 2026Review
Corrections and comments
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Authors and funding
22 authors.
Funding
Abstract
backgroundImmune aging may contribute to Alzheimer's disease. Bacillus Calmette-Guérin (BCG), a vaccine known to induce trained immunity, has been linked to reduced Alzheimer's risk in prior studies. However, whether trained immunity can be observed in the human central nervous system remains unclear. We assessed whether BCG induces trained immunity-like responses in adults with and without Alzheimer's-related changes.
methodsWe conducted two related one-year, open-label clinical trials in adults aged 55 years or older (n = 12 without Alzheimer's-related pathology; n = 11 with Alzheimer's-related pathology) recruited at a single center. Participants received two intradermal BCG vaccinations one month apart. Protocol-defined objectives included safety, neurocognitive outcomes, and longitudinal immune and Alzheimer's biomarker changes in blood and cerebrospinal fluid. Immune responses were assessed using cytokine assays and single-cell profiling. All enrolled participants were included where data were available; longitudinal changes were analyzed using mixed-effects models.
resultsHere we show that BCG induces persistent, trained immunity-like changes in immune cells in cerebrospinal fluid, including enhanced innate responsiveness and associated transcriptional programs. These responses differ from blood, suggesting compartment-specific immune imprinting. In participants without Alzheimer's-related changes, these immune shifts are accompanied by decreased amyloid-β levels in cerebrospinal fluid and increased levels in blood. BCG was well tolerated, with no unexpected safety signals observed.
conclusionsThese findings suggest trained immunity-like responses in the central nervous system that may influence Alzheimer's-relevant pathways. This approach may represent an early neurodegenerative intervention strategy, although larger controlled studies are needed to confirm these observations.
trial registrationClinicalTrials.gov NCT04507126 (June 23, 2020) and NCT05004688 (August 6, 2021).
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.