Affiliations: [a] Program on Cell and Neurobiology of Energy Metabolism, Section of Comparative Medicine, Yale University School of Medicine, New Haven, CT, USA | [b] Department of Biochemistry, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil | [c] Neuroscience Group, Instituto de Investigacion Hospital 12 de Octubre (i+12), Madrid, Spain | [d] Center for Networked Biomedical Research in Neurodegenerative Diseases (CIBERNED), Madrid, Spain
Correspondence:
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Correspondence to: Dr. Eva Carro, Neuroscience Group, Instituto de Investigacion Hospital 12 de Octubre (i+12), 28041 Madrid, Spain. Tel.: +34 913908765; Fax: +34 913908544; E-mail: carroeva@h12o.es.
Note: [1] Present address: Menzies Research Institute Tasmania, University of Tasmania, Hobart, Tasmania, Australia.
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.
