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. Author manuscript; available in PMC: 2023 Apr 20.
Published in final edited form as: Neuron. 2022 Mar 16;110(8):1304–1317. doi: 10.1016/j.neuron.2022.03.004

Figure 3. ApoE and cellular homeostasis.

Figure 3.

ApoE traffics through the secretory pathway as a non-lipidated or lipidated protein into the extracellular space. ABC transporters load membrane and traffic intracellular lipids onto apoE to produce nascent apoE/lipoprotein particles. ApoE-containing lipid particles can undergo further lipid modifications and are taken up by various cells through receptor-mediated endocytosis by binding to apoE receptors. This process supplies cells with diverse lipids including phospholipids and cholesterols necessary to maintain cellular homeostasis and support synaptic integrity and plasticity. The endocytosed particles and their components are transported to lysosome/autophagosome through late endosomes or recycled back to the extracellular space through recycling endosomes. ApoE isoforms impact cellular homeostasis by differentially modulating membrane trafficking, ER stress, and mitochondria function due to their individual effects on protein homeostasis, aggregation, and lipid metabolism.