Sexually dimorphic expression of reelin in a mouse model of Alzheimer disease

Reelin is a glycoprotein secreted in developing brain by Cajal-Retzius cells and mediates proper positioning of migrating neurons in cortical layers. Binding to apolipoprotein E receptor 2 (ApoER2) and very-lowdensity lipoprotein receptor (VLDLR) receptors, Reelin triggers a cytosolic kinase cascade leading to the activation of phosphatidylinositol-3-kinase (PI3K) and the inhibition of glycogen synthase kinase 3β (GSK3β). The latter is the major kinase of the microtubule- associated tau protein, which upon hyperphosphorylation aggregates forming the neurofibrillary tangles. In the adult brain, Reelin is produced by GABAergic interneurons and glutamatergic pyramidal neurons of layer II of the entorhinal cortex and regulating the activity of NMDA glutamate receptors plays a crucial role in synaptic plasticity. In agreement with this role, several studies indicate that a disregulation of the reelin-mediated signaling contribute to synaptic alteration and neuronal loss in mouse models of