Expression and alternate splicing of apolipoprotein E receptor 2 in brain

Apolipoprotein E isoforms affect the risk of developing Alzheimer's disease . Apolipoprotein E-associated risk may be related to its binding to and cle arance by cell surface receptors, including members of the low-density lipo protein receptor family. We examined the brain expression of the most recen tly identified member of this receptor family, apolipoprotein E receptor 2, in human brain and placenta. We analysed apolipoprotein E receptor 2 messe nger RNA by reverse transcription-polymerase chain reaction and apolipoprot ein E receptor 2 protein by immunohistochemistry. Four exons of the apolipo protein E receptor 2 message were alternately spliced in both fetal and adu lt brain tissue. Exon 5, encoding three of the seven ligand binding repeats , was absent in the apolipoprotein E receptor 2 messenger RNA examined. Apo lipoprotein E receptor 2 messages lacking exon 8, encoding an epidermal gro wth factor precursor repeat, exon 15, encoding the O-glycosylation region, or exon 18, encoding a cytoplasmic domain, were also present as minor splic e variants in the brain and placenta. No differences were observed in the p attern of apolipoprotein E receptor 2 splicing between control and Alzheime r brains. Immunohistochemistry of mouse brain showed that apolipoprotein E receptor 2 was expressed in neurons throughout the brain, with strong expre ssion in pyramidal neurons of the hippocampus, granule cells of the dentate gyrus, cortical neurons and Purkinje cells of the cerebellum. Thus, apolipoprotein E receptor 2 is the fourth apolipoprotein E receptor i dentified on neuronal cells. (C) 1999 IBRO. Published by Elsevier Science L td.