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Background Brain lipids such as cholesterol play critical roles in neuronal membrane homeostasis and synaptic functions. Apolipoprotein E (apoE) is a major lipid transporter in the brain. Of the three human apoE isoforms (E2, E3 and E4), apoE4 is a strong risk factor for late-onset Alzheimer’s disease (AD). Brain apoE/lipoprotein particles, produced primarily by astrocytes, deliver cholesterol and other lipids to neurons to support synapses via apoE receptors, which belong to the low-density lipoprotein receptor (LDLR) family. To ultimately understand why apoE4 is a risk factor for AD, it is essential to study the differential functions of apoE isoforms in brain lipid transport and synaptic functions, and what specific roles apoE receptors play in these processes.

ApoE and apoE receptors in brain lipid metabolism and AD