Regionally specific neuronal expression of human APOE gene in transgenic mice.

Apolipoprotein E (APOE, gene; apoE, protein) is a susceptibility gene for late-onset Alzheimer's disease (AD). To examine whether neurons can synthesize apoE, we performed in situ hybridization on brain tissue of transgenic mice carrying genomic constructs for the three major human APOE alleles. We find human APOE mRNA in glial cells of cerebellum, striatum and cerebral cortex and also in neurons of cerebral cortex, corresponding to apoE localization in humans. Synthesis of apoE by neurons implies that models of AD may need to consider intrinsic apoE production in addition to uptake. Inclusion of human regulatory sequences may result in more realistic transgenic models of human disease.