APOE4 affects basal and NMDAR mediated protein synthesis in neurons by perturbing calcium homeostasis

Abstract

Apolipoprotein E (APOE), one of the primary lipoproteins in the brain has three isoforms in humans –APOE2, APOE3, and APOE4. APOE4 is the most well-established risk factor increasing the predisposition for Alzheimer's disease. The presence of the APOE4 allele alone is shown to cause synaptic defects in neurons and recent studies have identified multiple pathways directly influenced by APOE4. However, the mechanisms underlying APOE4 induced synaptic dysfunction remain elusive. Here, we report that the acute exposure of primary cortical neurons or synaptoneurosomes to APOE4 leads to a significant decrease in global protein synthesis.