EXPRESSION OF THE VERY-LOW-DENSITY LIPOPROTEIN RECEPTOR (VLDL-R), AN APOLIPOPROTEIN-E RECEPTOR, IN THE CENTRAL-NERVOUS-SYSTEM AND IN ALZHEIMERS-DISEASE

The very low density lipoprotein receptor (VLDL-r) is a cell-surface m olecule specialized for the internalization of multiple diverse ligand s, including apolipoprotein E (apoE)-containing lipoprotein particles, via clathrin-coated pits. Its structure is similar to the low-density lipoprotein receptor (LDL-r), although the two have substantially dif ferent systemic distributions and regulatory pathways. The present wor k examines the distribution of VLDL-r in the central nervous system (C NS) and in relation to senile plaques in Alzheimer disease (AD). VLDL- r is present on resting and activated microglia, particularly those as sociated with senile plaques (SPs). VLDL-r immunoreactivity is also fo und in cortical neurons. Two exons of VLDL-r mRNA are differentially s pliced in the mature receptor mRNA. One set of splice forms gives rise to receptors containing (or lacking) an extracellular O-linked glycos ylation domain near the transmembrane portion of the molecule. The oth er set of splice forms appears to be brain-specific, and is responsibl e for the presence or absence of one of the cysteine-rich repeat regio ns in the binding region of the molecule. Ratios of the receptor varia nts generated from these splice forms do not differ substantially acro ss different cortical areas or in AD. We hypothesize that VLDL-r might contribute to metabolism of apoE and apoE/A beta complexes in the bra in. Further characterization of apoE receptors in Alzheimer brain may help lay the groundwork for understanding the role of apoE in the CNS and in the pathophysiology of AD.