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

Jin G. Sheng, Susan H. Bora, G. Xu, David R. Borchelt, Donald L. Price, Vassilis E. Koliatsos

Research output: Contribution to journalArticlepeer-review

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 β peptide (Aβ). APPswe transgenic (Tg) mice were treated with either LPS or phosphate-buffered saline (PBS). In LPS-treated APPswe mice, Aβ1-40/42 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 Aβ- and APP-immunoreactive neurons (Aβ(+) and APP(+) neurons) increased significantly in LPS-treated APPswe mice; APP(+) and Aβ(+) 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 Aβ. It remains to be seen whether such events can cause neuronal dysfunction/degeneration and, with time, lead to extracellular Aβ deposits, as they occur in Alzheimer's disease.

Original languageEnglish (US)
Pages (from-to)133-145
Number of pages13
JournalNeurobiology of Disease
Volume14
Issue number1
DOIs
StatePublished - Oct 2003

Keywords

  • APP processing
  • Alzheimer's disease
  • Intracellular Aβ
  • LPS
  • Microglia
  • Neuroinflammation
  • Transgenic mice

ASJC Scopus subject areas

  • Neurology

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