Significance of the variant and full-length forms of the very low density lipoprotein receptor in brain

The very low density lipoprotein receptor (VLDLR) is a newly described receptor which binds to apolipoprotein E (apoE) specifically. The authors designed a synthetic peptide of 17 amino acids representing the N-terminus of the putative first ligand binding domain of human VLDLR, this being a unique domain for VLDLR. When the synthetic peptide was used as the antigen, two different monoclonal antibodies were obtained (anti-VLDLR1 and anti-VLDLR2). Expressional cloning revealed that anti-VLDLR1 recognized the variant form of VLDLR which lacks 84 bp of O-linked sugar domain and anti-VLDLR2 recognized the full length form of VLDLR. The variant VLDLR was expressed in neuroblasts as well as matrix cells and Cajal-Retzius cells in the early stages of the developing human brain; later its expression was sequentially found in glioblasts, astrocytes, oligodendrocytes and finally in myelin. The expression of a full length form of VLDLR was detected in senile plaques and some neurons and satellite glia in aged and Alzheimer brains. This suggests that the variant VLDLR is important for the developing human brain and the full length VLDLR has modified functions in aged and Alzheimer brains.