Alzheimer's Disease-Like Impaired Cognition in Endothelial-Specific Megalin-Null Mice

作者：Dietrich Marcelo; Antequera Desiree; Pascual Consuelo; Castro Nerea; Bolos Marta; Carro Eva^*

来源：Journal of Alzheimer's Disease, 2014, 39(4): 711-717.

DOI：10.3233/JAD-131604

• Alzheimer's disease
• cognitive impairment
• memory
• neurodegeneration
• transgenic mice

Megalin has been suggested to be involved in Alzheimer's disease (AD), mediating blood-brain barrier (BBB) transport of multiple ligands, including amyloid-beta peptide (A beta), 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.

• 出版日期2014