Expression of the very low-density lipoprotein receptor (VLDL-r), an apolipoprotein-E receptor, in the central nervous system and in Alzheimer`s disease
- Massachusetts General Hospital, Boston, MA (United States); and others
The very low density lipoprotein receptor (VLDL-r) is a cell-surface molecule specialized for the internalization of multiple diverse ligands, 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 different systemic distributions and regulatory pathways. The present work examines the distribution of VLDL-r in the central nervous system (CNS) and in relation to senile plaques in Alzheimer disease (AD). VLDL-r is present on resting and activated microglia, particularly those associated with senile plaques (SPs). VLDL-r immunoreactivity is also found in cortical neurons. Two exons of VLDL-r mRNA are differentially spliced in the mature receptor mRNA. One set of splice forms gives rise to receptors containing (or lacking) an extracellular O-linked glycosylation domain near the transmembrane portion of the molecule. The other set of splice forms appears to be brain-specific, and is responsible for the presence or absence of one of the cysteine-rich repeat regions in the binding region of the molecule. Ratios of the receptor variants generated from these splice forms do not differ substantially across different cortical areas or in AD. We hypothesize that VLDL-r might contribute to metabolism of apoE and apoE/A{beta} complexes in the brain. 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. 43 refs., 5 figs.
- Sponsoring Organization:
- USDOE
- OSTI ID:
- 471506
- Journal Information:
- Journal of Neuropathology and Experimental Neurology, Vol. 55, Issue 4; Other Information: PBD: Apr 1996
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
BASIC STUDIES
APOLIPOPROTEINS
GENE REGULATION
RECEPTORS
STRUCTURE-ACTIVITY RELATIONSHIPS
TISSUE DISTRIBUTION
GENE MUTATIONS
METABOLISM
DNA SEQUENCING
NERVOUS SYSTEM DISEASES
PATHOLOGY
CENTRAL NERVOUS SYSTEM
MORPHOLOGY
PATIENTS
MENTAL DISORDERS
HEREDITARY DISEASES
MESSENGER-RNA
SPLICING
BRAIN
CYSTEINE
AMINO ACID SEQUENCE
POLYMERASE CHAIN REACTION