title: Alzheimer's disease-like impaired cognition in endothelial-specific megalin-null mice.
abstract: Megalin has been suggested to be involved in Alzheimer's disease (AD), mediating blood-brain barrier (BBB) transport of multiple ligands, including amyloid-β peptide (Aβ), but also neuroprotective factors. Because no transgenic model is currently available to study this concept, we have obtained transgenic mice blocking megalin expression at the BBB. These endothelial megalin deficient (EMD) mice developed increased anxiety behavior and impaired learning ability and recognition memory, similar to symptoms described in AD. Degenerating neurons were also observed in the cerebral cortex of EMD mice. In view of our findings we suggest that, in mice, megalin deficiency at the BBB leads to neurodegeneration.
authors.affiliation: Program on Cell and Neurobiology of Energy Metabolism, Section of Comparative Medicine, Yale University School of Medicine, New Haven, CT, USA Department of Biochemistry, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
authors.forename: Marcelo
authors.initials: M
authors.lastname: Dietrich
authors.affiliation: Neuroscience Group, Instituto de Investigacion Hospital 12 de Octubre (i+12), Madrid, Spain Center for Networked Biomedical Research in Neurodegenerative Diseases (CIBERNED), Madrid, Spain.
authors.forename: Desiree
authors.initials: D
authors.lastname: Antequera
authors.affiliation: Neuroscience Group, Instituto de Investigacion Hospital 12 de Octubre (i+12), Madrid, Spain Center for Networked Biomedical Research in Neurodegenerative Diseases (CIBERNED), Madrid, Spain.
authors.forename: Consuelo
authors.initials: C
authors.lastname: Pascual
authors.affiliation: Neuroscience Group, Instituto de Investigacion Hospital 12 de Octubre (i+12), Madrid, Spain Center for Networked Biomedical Research in Neurodegenerative Diseases (CIBERNED), Madrid, Spain.
authors.forename: Nerea
authors.initials: N
authors.lastname: Castro
authors.affiliation: Neuroscience Group, Instituto de Investigacion Hospital 12 de Octubre (i+12), Madrid, Spain Center for Networked Biomedical Research in Neurodegenerative Diseases (CIBERNED), Madrid, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Bolos
authors.affiliation: Neuroscience Group, Instituto de Investigacion Hospital 12 de Octubre (i+12), Madrid, Spain Center for Networked Biomedical Research in Neurodegenerative Diseases (CIBERNED), Madrid, Spain.
authors.forename: Eva
authors.initials: E
authors.lastname: Carro
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D002478:Cells, Cultured; D003072:Cognition Disorders / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D042783:Endothelial Cells / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D026561:Low Density Lipoprotein Receptor-Related Protein-2 / Q000172:deficiency* / Q000235:genetics; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic
chemical_list: D026561:Low Density Lipoprotein Receptor-Related Protein-2; C055127:Lrp2 protein, mouse
keywords: Alzheimer's disease; cognitive impairment; memory; neurodegeneration; transgenic mice