title: Absence of apolipoprotein E protects mice from cerebral malaria.
abstract: Cerebral malaria claims the life of millions of people each year, particularly those of children, and is a major global public health problem. Thus, the identification of novel malaria biomarkers that could be utilized as diagnostic or therapeutic targets is becoming increasingly important. Using a proteomic approach, we previously identified unique biomarkers in the sera of malaria-infected individuals, including apolipoprotein E (ApoE). ApoE is the dominant apolipoprotein in the brain and has been implicated in several neurological disorders; therefore, we were interested in the potential role of ApoE in cerebral malaria. Here we report the first demonstration that cerebral malaria is markedly attenuated in ApoE(-/-) mice. The protection provided by the absence of ApoE was associated with decreased sequestration of parasites and T cells within the brain, and was determined to be independent from the involvement of ApoE receptors and from the altered lipid metabolism associated with the knock-out mice. Importantly, we demonstrated that treatment of mice with the ApoE antagonist heparin octasaccharide significantly decreased the incidence of cerebral malaria. Overall, our study indicates that the reduction of ApoE could be utilized in the development of therapeutic treatments aimed at mitigating the neuropathology of cerebral malaria.
authors.affiliation: Department of Medicine, Microbiology and Immunology, Faculty of Medicine, McGill University, Montréal, Québec, Canada.|The Research Institute of the McGill University Health Centre and Infectious Diseases and Immunity in Global Health Program, Montréal, Québec, Canada.
authors.forename: Fikregabrail Aberra
authors.initials: FA
authors.lastname: Kassa
authors.affiliation: Department of Medicine, Microbiology and Immunology, Faculty of Medicine, McGill University, Montréal, Québec, Canada.|The Research Institute of the McGill University Health Centre and Infectious Diseases and Immunity in Global Health Program, Montréal, Québec, Canada.
authors.forename: Kristin
authors.initials: K
authors.lastname: Van Den Ham
authors.affiliation: Department of Medicine, Microbiology and Immunology, Faculty of Medicine, McGill University, Montréal, Québec, Canada.
authors.forename: Anthony
authors.initials: A
authors.lastname: Rainone
authors.affiliation: Department of Medicine, Microbiology and Immunology, Faculty of Medicine, McGill University, Montréal, Québec, Canada.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Fournier
authors.affiliation: Centre de Recherche du Centre Hospitalier Universitaire de Québec, Université Laval, Québec, Québec, Canada.
authors.forename: Eric
authors.initials: E
authors.lastname: Boilard
authors.affiliation: Department of Medicine, Microbiology and Immunology, Faculty of Medicine, McGill University, Montréal, Québec, Canada.|The Research Institute of the McGill University Health Centre and Infectious Diseases and Immunity in Global Health Program, Montréal, Québec, Canada.
authors.forename: Martin
authors.initials: M
authors.lastname: Olivier
mesh_terms: D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency*; D001812:Blood-Brain Barrier / Q000378:metabolism; D001921:Brain / Q000276:immunology / Q000378:metabolism / Q000469:parasitology; D016207:Cytokines / Q000097:blood / Q000378:metabolism; D004195:Disease Models, Animal; D060467:Disease Resistance / Q000235:genetics*; D005473:Fluoxetine / Q000494:pharmacology; D017353:Gene Deletion; D020022:Genetic Predisposition to Disease; D018836:Inflammation Mediators / Q000097:blood / Q000378:metabolism; D050356:Lipid Metabolism; D026503:Low Density Lipoprotein Receptor-Related Protein-1 / Q000378:metabolism; D016779:Malaria, Cerebral / Q000235:genetics* / Q000276:immunology / Q000401:mortality / Q000469:parasitology*; D051379:Mice; D018345:Mice, Knockout; D059208:Parasite Load; D050486:Serotonin Plasma Membrane Transport Proteins / Q000172:deficiency; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism
chemical_list: D001057:Apolipoproteins E; D016207:Cytokines; D018836:Inflammation Mediators; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D050486:Serotonin Plasma Membrane Transport Proteins; D005473:Fluoxetine