Persistent microbial material contributes to Alzheimer disease and is targetable by vaccination

Marcet, E. C.; Vinacur, M.; Zaidi, T.; Nguyen, N.; Augart-Welwood, A.; Su, G.; Landau, D.; LaVancher, E.; Arkhangelskiy, A.; Power, L. H.; Kelly, M. E.; Stein, C. R.; Carolan, E.; Caldarone, B.; Lemere, C. A.; Wasen, C.; Cox, L. M.; Cairns, D. M.; Kaplan, D.; Pier, G. B.; Cywes-Bentley, C.

doi:10.64898/2026.07.20.739171

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bioRxiv · 10.64898/2026.07.20.739171

Persistent microbial material contributes to Alzheimer disease and is targetable by vaccination

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Abstract

Chronic neuroinflammation is increasingly recognized as a contributor to Alzheimer disease, yet the upstream stimuli that sustain it remain poorly defined. We investigated whether persistent microbial material contributes to Alzheimer disease using the conserved microbial polysaccharide poly-N-acetylglucosamine (PNAG). PNAG-containing microbial material colocalized with amyloid plaques in human Alzheimer disease brain tissue. In fully human neuronal and three-dimensional brain models, purified PNAG and PNAG-containing microbial vesicles activated Toll-like receptor 2-dependent inflammasome signaling and promoted amyloid-{beta} and phosphorylated tau accumulation. Vaccination targeting PNAG improved cognition, reduced glial activation and amyloid pathology, remodeled amyloid processing, and preserved gut microbial community structure in APP/PS1 mice. These findings identify persistent microbial material as an upstream contributor to Alzheimer disease-associated neuroinflammation and a potential therapeutic target.

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Marcet, E. C., Vinacur, M., Zaidi, T., Nguyen, N., Augart-Welwood, A., Su, G., Landau, D., LaVancher, E., Arkhangelskiy, A., Power, L. H., Kelly, M. E., Stein, C. R., Carolan, E., Caldarone, B., Lemere, C. A., Wasen, C., Cox, L. M., Cairns, D. M., Kaplan, D., Pier, G. B., Cywes-Bentley, C.. 2026-07-23. Persistent microbial material contributes to Alzheimer disease and is targetable by vaccination. https://doi.org/10.64898/2026.07.20.739171

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