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 language | English (US) |
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Pages (from-to) | 133-145 |
Number of pages | 13 |
Journal | Neurobiology of Disease |
Volume | 14 |
Issue number | 1 |
DOIs | |
State | Published - Oct 2003 |
Keywords
- APP processing
- Alzheimer's disease
- Intracellular Aβ
- LPS
- Microglia
- Neuroinflammation
- Transgenic mice
ASJC Scopus subject areas
- Neurology