Intrahippocampal LPS injections reduce Abeta load in APP+PS1 transgenic mice.
Multiple lines of evidence indicate that inflammatory processes are involved in the pathogenesis of Alzheimer's disease. Lipopolysaccharide (LPS) is widely used to induce inflammation in experimental systems. Consequently we injected LPS or saline intrahippocampally in 11 and 16 months old APP+PS1 transgenic mice to induce brain inflammation, then used immunocytochemistry to examine amyloid pathology 7 days later. As expected, LPS activated microglia as indicated by a significant increase in the area covered by major histocompatibility complex-II (MHC-II) immunostaining in the mice injected with LPS compared to the saline injected. Simultaneously, Abeta immunostaining showed an unexpected reduction of the Abeta load in the mice injected with LPS compared to the saline injected. This effect of LPS on the Abeta load in APP+PS1 mice strengthens the hypothesis that moderate amounts of microglial activation may be beneficial in Alzheimer's disease, by increasing the clearance of Abeta.
DiCarlo
G
G
Department of Pharmacology, Alzheimer's research Laboratory, University of South Florida, Tampa, Florida 33612, USA.
Wilcock
D
D
Henderson
D
D
Gordon
M
M
Morgan
D
D
D016229:Amyloid beta-Peptides / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics* / Q000378:metabolism*; D000818:Animals; D005786:Gene Expression Regulation / Q000187:drug effects; D005802:Genes, MHC Class II / Q000235:genetics; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D007150:Immunohistochemistry; D008070:Lipopolysaccharides / Q000008:administration & dosage / Q000494:pharmacology*; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D017628:Microglia / Q000187:drug effects / Q000473:pathology; D008845:Microinjections; D053764:Presenilin-1
D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D008070:Lipopolysaccharides; D008565:Membrane Proteins; D053764:Presenilin-1