Lipopolysaccharide-induced-neuroinflammation increases intracellular accumulation of amyloid precursor protein and amyloid β peptide in APPswe transgenic mice
JG Sheng, SH Bora, G Xu, DR Borchelt, DL Price… - Neurobiology of …, 2003 - Elsevier
JG Sheng, SH Bora, G Xu, DR Borchelt, DL Price, VE Koliatsos
Neurobiology of disease, 2003•ElsevierThe 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 …
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 …
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.
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