Apolipoprotein E (APOE) is the primary lipid transport protein in the brain and the strongest common genetic risk factor for late-onset Alzheimer's disease. APOE is produced predominantly by astrocytes, which use it to package and deliver cholesterol and lipids to neurons — a process essential for synaptic maintenance, membrane repair, and neuronal resilience.

The APOE4 allele has been associated with impaired lipid and cholesterol transport, heightened neuroinflammatory signaling, reduced capacity for synaptic support, and increased cellular stress responses in astrocytes compared to APOE3 counterparts. These phenotypic differences are biologically meaningful and have been documented across human cell-based and transcriptomic studies.

iPSC-derived or genetically edited astrocytes require differentiation workflows that may introduce developmental immaturity. Primary human astrocytes from donors with confirmed APOE genotype preserve the native cellular context in which these differences are expressed.