Expression of the very low-density lipoprotein receptor (VLDL-r), an apolipoprotein-E receptor, in the central nervous system and in Alzheimer's disease.

Full Abstract

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 characterizations 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.

Author information

Author/s: Christie, R H (RH); Chung, H (H); Rebeck, G W (GW); Strickland, D (D); Hyman, B T (BT);

Affiliation: Neurology Service, Massachusetts General Hospital, Boston, Massachusetts 02114, USA.

Grants: AG08487 (Agency:NIA NIH HHS) ; AG12406 (Agency:NIA NIH HHS) ; GM42581 (Agency:NIGMS NIH HHS)

Journal and publication information

Publication Type: Journal Article; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S.

Journal: Journal of neuropathology and experimental neurology (J Neuropathol Exp Neurol), published in UNITED STATES. (Language: eng)

Reference: 1996-Apr; vol 55 (issue 4) : pp 491-8

Dates: Created 1996/09/20; Completed 1996/09/20; Revised 2007/11/14;

PMID: 8786409, status: MEDLINE (last retrieved date: 2/18/2009)

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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