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 ca n synthesize apoE, we performed in situ hybridization on brain tissue of transgenic mice carrying genomic constructs for the three major hum an 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 neu rons implies that models of AD may need to consider intrinsic apoE pro duction in addition to uptake. Inclusion of human regulatory sequences may result in more realistic transgenic models of human disease. (C) 1998 Published by Elsevier Science Ireland Ltd.