Cited by 389Alzheimer's disease research and treatmentsNeuroinflammation and Neurodegeneration MechanismsAnesthesia and Neurotoxicity Research

Lipopolysaccharide-induced-neuroinflammation increases intracellular accumulation of amyloid precursor protein and amyloid β peptide in APPswe transgenic mice

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Sheng, J·2003·Neurobiology of Disease

Abstract

The present study was designed to examine whether brain inflammation caused by systemic administration of lipopolysaccharides (LPS) alters the expression/processing of amyloid precursor protein (APP) and increases the generation of amyloid beta peptide (Abeta). APPswe transgenic (Tg) mice were treated with either LPS or phosphate-buffered saline (PBS). In LPS-treated APPswe mice, Abeta1-40/42 was 3-fold and APP was 1.8-fold higher than those in PBS-treated mice (P < 0.05) by ELISA, Western blots and immunoprecipitation-mass spectrometry (IP-MS) ProteinChip analysis. Numbers of Abeta- and APP-immunoreactive neurons (Abeta(+) and APP(+) neurons) increased significantly in LPS-treated APPswe mice; APP(+) and Abeta(+) neurons in neocortex were associated with an increased number of F4/80-immunoreactive microglia (F4/80(+) microglia) in their anatomical environment. Our findings demonstrate that experimental neuroinflammation increases APP expression/processing and causes intracellular accumulation of Abeta. It remains to be seen whether such events can cause neuronal dysfunction/degeneration and, with time, lead to extracellular Abeta deposits, as they occur in Alzheimer's disease.

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Crossref · 10.1016/s0969-9961(03)00069-x

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  • Nonspecific microglia activation induced by lipopolysaccharide does not have the same amyloid-promoting effect as myelin dysfunction, as increases, decreases or no changes in amyloid burden have been reported.

    “However, nonspecific microglia activation induced by lipopolysaccharide does not have the same amyloid-promoting effect as myelin dysfunction, as increases, decreases or no changes in amyloid burden have been reported48–51.”
  • LPS-induced inflammation in mice with amyloidosis or tauopathy increased neuropathology.

    “lipopolysaccharide (a major gram negative bacterial cell wall component)-induced inflammation in mice with amyloidosis or tauopathy increased neuropathology [187, 283]”

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Authors
Sheng, J.
Affiliations
Johns Hopkins University (US)
Corresponding author
Sheng, J
Venue
Neurobiology of Disease
Publisher
Elsevier BV
Published
2003-10
Volume
14
Issue
1
Pages
133-145
ISSN
0969-9961 (ISSN-L)
OpenAlex
W2023136593
Cited by
388
References
51
Citations by year
2026: 6 · 2025: 18 · 2024: 17 · 2023: 18 · 2022: 27 · 2021: 26 · 2020: 23 · 2019: 15 · 2018: 23 · 2017: 14 · 2016: 24 · 2015: 18 · 2014: 20 · 2013: 18 · 2012: 26
FWCI
6.71
Type
journal article
Language
en
Open access
Locations
  • Neurobiology of Disease (publishedVersion)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • National Institutes of Health
  • National Institute on Aging (P50AG005146, AG 05146)
  • National Institute of Neurological Disorders and Stroke (T32NS07435, T32NS007435)
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
  • Life Sciences › Neuroscience › Developmental Neuroscience › Anesthesia and Neurotoxicity Research
Keywords
lipopolysaccharide, neuroinflammation, amyloid precursor protein, amyloid-beta, microglia, F4/80, APP processing, Alzheimer's disease, neocortex
MeSH terms
Alzheimer Disease, Animals, Encephalitis, Intracellular Fluid, Lipopolysaccharides, Mice, Inbred C3H, Mice, Inbred C57BL, Mice, Transgenic, Peptide Fragments, Amyloid beta-Peptides, Amyloid beta-Protein Precursor, Mice

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