The DOI matches its Crossref record; 30 of the 30 references it cites were found in a registry or an index.
Gram-negative bacterial molecules associate with Alzheimer disease pathology
Open accessAbstract
Objective: We determined whether Gram-negative bacterial molecules are associated with Alzheimer disease (AD) neuropathology given that previous studies demonstrate Gram-negative Escherichia coli bacteria can form extracellular amyloid and Gram-negative bacteria have been reported as the predominant bacteria found in normal human brains. Methods: Brain samples from gray and white matter were studied from patients with AD (n = 24) and age-matched controls (n = 18). Lipopolysaccharide (LPS) and E coli K99 pili protein were evaluated by Western blots and immunocytochemistry. Human brain samples were assessed for E coli DNA followed by DNA sequencing. Results: LPS and E coli K99 were detected immunocytochemically in brain parenchyma and vessels in all AD and control brains. K99 levels measured using Western blots were greater in AD compared to control brains (p < 0.01) and K99 was localized to neuron-like cells in AD but not control brains. LPS levels were also greater in AD compared to control brain. LPS colocalized with Aβ1-40/42 in amyloid plaques and with Aβ1-40/42 around vessels in AD brains. DNA sequencing confirmed E coli DNA in human control and AD brains. Conclusions: E coli K99 and LPS levels were greater in AD compared to control brains. LPS colocalized with Aβ1-40/42 in amyloid plaques and around vessels in AD brain. The data show that Gram-negative bacterial molecules are associated with AD neuropathology. They are consistent with our LPS-ischemia-hypoxia rat model that produces myelin aggregates that colocalize with Aβ and resemble amyloid-like plaques.
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“E. coli particles and LPS particles have been shown to associate directly with pathology in the brains of AD patients [41].”
From Alzheimer’s disease-associated protective variant Plcg2-P522R modulates peripheral macrophage function in a sex-dimorphic manner (2024) · cites this paper as [41]
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“Blood and brain endotoxin levels are elevated in Alzheimer’s disease”
From The endotoxin hypothesis of neurodegeneration (2019) · cites this paper as [79]
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“Brain endotoxin levels are increased two- or threefold in AD patients [78, 79], and endotoxin is also found in AD amyloid plaques [79].”
From The endotoxin hypothesis of neurodegeneration (2019) · cites this paper as [79]
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“There is a large increase in bacterial load and bacterial species in AD brains [79, 90], including P. gingivalis, which can live intracellularly in glia and neurons [91].”
From The endotoxin hypothesis of neurodegeneration (2019) · cites this paper as [79]
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“A variety of genetic and environmental factors have been implicated in AD etiopathogenesis, including contributions from gut microbiota [13–15].”
From The gut microbiota-derived metabolite trimethylamine N-oxide is elevated in Alzheimer’s disease (2018) · cites this paper as [14]
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Cites
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Serum IgG Antibody Levels to Periodontal Microbiota Are Associated with Incident Alzheimer Disease
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Gut microbiome alterations in Alzheimer’s disease
Vogt, N. M., Kerby, R. L., Dill-McFarland, K. A., Harding, S. J., Merluzzi, A. P., Johnson, S. C., Carlsson, C. M., Asthana, S., Zetterberg, H., Blennow, K., et al. (2017) · Scientific Reports · doi:10.1038/s41598-017-13601-y · Cited by 2,137
A systemic view of Alzheimer disease — insights from amyloid-β metabolism beyond the brain
Wang, J., Gu, B. J., Masters, C. L., & Wang, Y.-J. (2017) · Nature Reviews Neurology · doi:10.1038/nrneurol.2017.111 · Cited by 808
Liu, P., Wu, L., Peng, G., Han, Y., Tang, R., Ge, J., Zhang, L., Jia, L., Yue, S., Zhou, K., et al. (2019) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2019.05.008 · Cited by 669
Kim, M.-S., Kim, Y., Choi, H., Kim, W., Park, S., Lee, D., Kim, D. K., Kim, H. J., Choi, H., Hyun, D.-W., et al. (2020) · Gut · doi:10.1136/gutjnl-2018-317431 · Cited by 614
Inflammation: the link between comorbidities, genetics, and Alzheimer’s disease
Newcombe, E. A., Camats-Perna, J., Silva, M. L., Valmas, N., Huat, T. J., & Medeiros, R. (2018) · Journal of Neuroinflammation · doi:10.1186/s12974-018-1313-3 · Cited by 532
Metadata
- Authors
- Zhan, X., Stamova, B., Jin, L.-W., DeCarli, C., Phinney, B., & Sharp, F. R.
- Affiliations
- University of California Davis Medical Center (US)
- Corresponding author
- Zhan, Xinhua
- Venue
- Neurology
- Published
- 2016-11-29
- Volume
- 87
- Issue
- 22
- Pages
- 2324-2332
- ISSN
- 0028-3878 (ISSN-L)
- 1526-632X
- PMC
- PMC5135029
- OpenAlex
- W2545292312
- Cited by
- 521
- References
- 30
- Citations by year
- 2026: 38 · 2025: 41 · 2024: 69 · 2023: 49 · 2022: 69 · 2021: 86 · 2020: 75 · 2019: 40 · 2018: 30 · 2017: 24
- FWCI
- 25.23
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by-nc-nd
- Locations
- Neurology (publishedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion, cc-by-nc-nd)
- Funders
- National Institute on Aging (R01AG042292)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- Alzheimer's disease, Gram-negative bacteria, Escherichia coli, lipopolysaccharide, amyloid plaques, amyloid-beta, neuroinflammation
- MeSH terms
- Aged, Aged, 80 and over, Alzheimer Disease, Brain, DNA, Bacterial, Escherichia coli, Female, Fluorescent Antibody Technique, Humans, Lipopolysaccharides, Male, Peptide Fragments, Blotting, Western, Polymerase Chain Reaction, Amyloid beta-Peptides, Sequence Analysis, DNA, Escherichia coli Proteins, Plaque, Amyloid, White Matter, Gray Matter
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