NMDA receptor and <i>APOE</i> in Alzheimer’s disease: searching for connections

Background NMDA receptor (NMDAR) malfunctioning has been claimed as a crucial event in Alzheimer’s disease (AD), the most common form of dementia. While synaptic NMDAR activation leads to plasticity, extrasynaptic excitotoxicity, mitotoxicity and cell death. In late onset AD, APOE4 allele is main genetic risk factor. Our aim study influence apoE4 on function. Method We isolated membranes from APOE genotyped frontal cortex samples, AD non-demented subjects. studied levels subunits GluN2B GluN2A. also evaluated phosphorylation at sites Y1472 Y1336, associated membrane location, respectively. are developing hiPSC-derived cortical neurons non-AD Result At membranes, we found lower GluN2B, Glun2A pY1472-GluN2B respect patients. Inside group, APOE4-frontal showed non-APOE4. no changes were observed, but Y1336-GluN2B was higher that control. These results suggest more likely be where specific retain these those membranes. The lowest synapsis Conclusion seems compromise different manner vs try understand mechanisms govern status using iPSC-derived neurons. Understansing relation between apoE could lead new therapteutical approaches.