The LPS receptor (CD14) links innate immunity with Alzheimer's disease
Open accessAbstract
To rapidly respond to invading microorganisms, humans call on their innate immune system. This occurs by microbe‐detecting receptors, such as CD14, that activate immune cells to eliminate the pathogens. Here, we link the lipopolysaccharide receptor CD14 with Alzheimer's disease, a severe neurodegenerative disease resulting in dementia. We demonstrate that this key innate immunity receptor interacts with fibrils of Alzheimer amyloid peptide. Neutralization with antibodies against CD14 and genetic deficiency for this receptor significantly reduced amyloid peptide induced microglial activation and microglial toxicity. The observation of strongly enhanced microglial expression of the LPS receptor in brains of animal models of Alzheimer's disease indicates a clinical relevance of these findings. These data suggest that CD14 may significantly contribute to the overall neuroinflammatory response to amyloid peptide, highlighting the possibility that the enormous progress currently being made in the field of innate immunity could be extended to research on Alzheimer's disease.
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TLR4 activation induces NF-κB nuclear translocation, leading to production of proinflammatory mediators.
“TLR4 activation induced NF-κB nuclear translocation, leading to the production of proinflammatory mediators [370].”
From Molecular and cellular mechanisms underlying the pathogenesis of Alzheimer’s disease (2020) · cites this paper as [370]
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Self-citation
- Authors
- Fassbender, K., Walter, S., Kühl, S., Landmann, R., Ishii, K., Bertsch, T., Stalder, A. K., Muehlhauser, F., Liu, Y., Ulmer, A. J., Rivest, S., Lentschat, A., Gulbins, E., Jucker, M., Staufenbiel, M., Brechtel, K., Walter, J., Multhaup, G., Penke, B., Adachi, Y., Hartmann, T., & Beyreuther, K.
- Affiliations
- University of Göttingen (DE)
- Heidelberg University (DE)
- University Hospital of Basel (CH)
- Research Center Borstel - Leibniz Lung Center (DE)
- Université Laval (CA)
- St. Jude Children's Research Hospital (US)
- Novartis (Switzerland) (CH)
- Department of Neurology University of Goettingen 37075 Goettingen Germany
- University of Szeged (HU)
- Tokyo University of Pharmacy and Life Sciences (JP)
- ORCID
- Venue
- The FASEB Journal
- Publisher
- Wiley
- Published
- 2003-11-03
- Volume
- 18
- Issue
- 1
- Pages
- 203-205
- ISSN
- 0892-6638 (ISSN-L)
- 1530-6860
- OpenAlex
- W2149399096
- Cited by
- 307
- References
- 37
- Citations by year
- 2026: 4 · 2025: 4 · 2024: 9 · 2023: 3 · 2022: 7 · 2021: 13 · 2020: 13 · 2019: 14 · 2018: 10 · 2017: 17 · 2016: 15 · 2015: 7 · 2014: 15 · 2013: 17 · 2012: 14
- FWCI
- 9.72
- Type
- journal article
- Language
- en
- Open access
- Licence
- Locations
- The FASEB Journal (publishedVersion)
- PubMed (publishedVersion)
- GoeScholar The Publication Server of the Georg-August-Universität Göttingen (Georg-August-Universität Göttingen) (submittedVersion, other-oa)
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Inflammasome and immune disorders
- Keywords
- CD14, lipopolysaccharide receptor, Alzheimer's disease, innate immunity, amyloid-beta fibrils, microglial activation, neuroinflammation, anti-CD14 antibody, neurodegeneration
- MeSH terms
- Alzheimer Disease, Animals, Antibodies, Monoclonal, Immunity, Innate, Mice, Transgenic, Peptide Fragments, Amyloid beta-Peptides, Amyloid beta-Protein Precursor, Microglia, Mice, Knockout, Lipopolysaccharide Receptors, Mice
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