Borrelia burgdorferi Co-Localizing with Amyloid Markers in Alzheimer’s Disease Brain Tissues
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Background: Infections by bacterial or viral agents have been hypothesized to influence the etiology of neurodegenerative diseases. Objective: This study examined the potential presence of Borrelia burgdorferi spirochete, the causative agent of Lyme disease, in brain autopsy tissue of patients diagnosed with either Alzheimer’s (AD) or Parkinson’s diseases. Methods: Brain tissue sections from patients with age-matched controls were evaluated for antigen and DNA presence of B. burgdorferi using various methods. Positive Borrelia structures were evaluated for co-localization with biofilm and AD markers such as amyloid and phospho-tau (p-Tau) using immunohistochemical methods. Results: The results showed the presence of B. burgdorferi antigen and DNA in patients with AD pathology and among those, one of them was previously diagnosed with Lyme disease. Interestingly, a significant number of Borrelia-positive aggregates with a known biofilm marker, alginate, were found along with the spirochetal structures. Our immunohistochemical data also showed that Borrelia-positive aggregates co-localized with amyloid and phospho-tau markers. To further prove the potential relationship of B. burgdorferi and amyloids, we infected two mammalian cell lines with B. burgdorferi which resulted in a significant increase in the expression of amyloid-β and p-Tau proteins in both cells lines post-infection. Conclusion: These results indicate that B. burgdorferi can be found in AD brain tissues, not just in spirochete but a known antibiotics resistant biofilm form, and its co-localized amyloid markers. In summary, this study provides evidence for a likely association between B. burgdorferi infections and biofilm formation, AD pathology, and chronic neurodegenerative diseases.
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In human AD brains, B. burgdorferi DNA and antigens have been found in senile plaques and are highly co-localized with both amyloid protein and phospho-tau in the cerebral cortex.
“In human AD brains, B. burgdorferi DNA and antigens have been found in senile plaques and are highly co-localized with both amyloid protein and phospho-tau in the cerebral cortex [64,65].”
From What would it take to prove that a chronic infection is a causal agent in Alzheimer’s disease? (2025) · cites this paper as [65]
The Results report B. burgdorferi DNA in two AD brain samples and show Borrelia-positive aggregates co-localizing with amyloid and phospho-tau markers in sections from one patient with AD and Lyme disease. They do not show that the DNA itself was located in senile plaques, or establish that the reported co-localization was specifically in the cerebral cortex; “highly” also goes beyond the reported finding. (LLM, conf=0.86)
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Knopman, D. S., Amieva, H., Petersen, R. C., Chételat, G., Holtzman, D. M., Hyman, B. T., Nixon, R. A., & Jones, D. T. (2021) · Nature Reviews Disease Primers · doi:10.1038/s41572-021-00269-y · Cited by 2,606 · see citing works
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What would it take to prove that a chronic infection is a causal agent in Alzheimer’s disease?
Brutkiewicz, R. R., Cao, W., Morgan, D., Reis, R. S. D., Suryadevara, V., Willette, A. A., Willette, S. A., Wyatt-Johnson, S. K., & Duggan, M. R. (2025) · Trends in Neurosciences · doi:10.1016/j.tins.2025.05.009 · Cited by 3 · see citing works
- Authors
- Senejani, A. G., Maghsoudlou, J., El-Zohiry, D., Gaur, G., Wawrzeniak, K., Caravaglia, C., Khatri, V. A., MacDonald, A., & Sapi, E.
- Affiliations
- University of New Haven (US)
- Molecular Interrogation Research Laboratory, Naples, FL, USA
- Corresponding author
- Senejani, Alireza G.
- Venue
- Journal of Alzheimer's Disease
- Publisher
- SAGE Publications
- Published
- 2022-01-18
- Volume
- 85
- Issue
- 2
- Pages
- 889-903
- ISSN
- 1387-2877 (ISSN-L)
- 1875-8908
- PMC
- PMC8842785
- OpenAlex
- W4200322410
- Cited by
- 40
- References
- 1
- Citations by year
- 2026: 6 · 2025: 10 · 2024: 10 · 2023: 7 · 2022: 7
- FWCI
- 3.76
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Alzheimer s Disease (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- Funders
- National Philanthropic Trust
- University of Connecticut
- Global Lyme Alliance
- National Institutes of Health (1s10od016435-01a1)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Immunology and Microbiology › Parasitology › Vector-borne infectious diseases
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- Borrelia burgdorferi, Lyme disease
- MeSH terms
- Aged, Alzheimer Disease, Amyloidosis, Brain, DNA, Bacterial, Humans, Biomarkers, tau Proteins, Biofilms, Lyme Neuroborreliosis, Borrelia burgdorferi, Cell Line, Tumor, Amyloidogenic Proteins
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