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: Marcelo Dietrich, Desiree Antequera, Consuelo Pascual, Nerea Castro, Marta Bolos, Eva Carro
• Journal: Journal of Alzheimer's disease : JAD (J Alzheimers Dis) Vol. 39 Issue 4 Pg. 711-7 ( 2014) ISSN: 1875-8908 [Electronic] Netherlands
• PMID: 24254699 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Low Density Lipoprotein Receptor-Related Protein-2
• Lrp2 protein, mouse

Topics

• Alzheimer Disease (genetics, metabolism, pathology)
• Animals
• Cells, Cultured
• Cognition Disorders (genetics, metabolism, pathology)
• Endothelial Cells (metabolism, pathology)
• Humans
• Low Density Lipoprotein Receptor-Related Protein-2 (deficiency, genetics)
• Male
• Mice
• Mice, Knockout
• Mice, Transgenic