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Phenotypes of apolipoprotein B and apolipoprotein E after liver transplantation.
Open accessAbstract
Apolipoprotein (apo) E and the two B apolipoproteins, apoB48 and apoB100, are important proteins in human lipoprotein metabolism. Commonly occurring polymorphisms in the genes for apoE and apoB result in amino acid substitutions that produce readily detectable phenotypic differences in these proteins. We studied changes in apoE and apoB phenotypes before and after liver transplantation to gain new insights into apolipoprotein physiology. In all 29 patients that we studied, the postoperative serum apoE phenotype of the recipient, as assessed by isoelectric focusing, converted virtually completely to that of the donor, providing evidence that greater than 90% of the apoE in the plasma is synthesized by the liver. In contrast, the cerebrospinal fluid apoE phenotype did not change to the donor's phenotype after liver transplantation, indicating that most of the apoE in CSF cannot be derived from the plasma pool and therefore must be synthesized locally. The apoB100 phenotype (assessed with immunoassays using monoclonal antibody MB19, an antibody that detects a two-allele polymorphism in apoB) invariably converted to the phenotype of the donor. In four normolipidemic patients, we determined the MB19 phenotype of both the apoB100 and apoB48 in the "chylomicron fraction" isolated from plasma 3 h after a fat-rich meal. Interestingly, the apoB100 in the chylomicron fraction invariably had the phenotype of the donor, indicating that the vast majority of the large, triglyceride-rich apoB100-containing lipoproteins that appear in the plasma after a fat-rich meal are actually VLDL of hepatic origin. The MB19 phenotype of the apoB48 in the plasma chylomicron fraction did not change after liver transplantation, indicating that almost all of the apoB48 in plasma chylomicrons is derived from the intestine. These results were consistent with our immunocytochemical studies on intestinal biopsy specimens of organ donors; using apoB-specific monoclonal antibodies, we found evidence for apoB48, but not apoB100, in donor intestinal biopsy specimens.
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“ApoE found in the periphery and the central nervous system (CNS) are independent of each other and produced from different sources [3].”
From In Vivo Human Apolipoprotein E Isoform Fractional Turnover Rates in the CNS (2012) · cites this paper as [3]
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“A limited blood brain barrier permeability to circulating lipidpoor apoE2, apoE3, and apoE4 supports that apoE in blood and brain are regulated independently [72,107,108].”
From Plasma levels of apolipoprotein E, APOE genotype and risk of dementia and ischemic heart disease: A review (2016) · cites this paper as [72]
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“ApoE in the brain and CSF is synthesized within the central nervous system and is not derived from other organs.13”
From ApoE is Secreted as a Lipid Nanoparticle by Mammalian Cells: Implications for Alzheimer’s Disease Pathogenesis (2025) · cites this paper as [13]
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“APOE circulating in the blood is predominantly produced by the liver; however, the BBB keeps this pool of peripheral APOE separated from that produced in the CNS181,182.”
From Multifaceted roles of APOE in Alzheimer disease (2024) · cites this paper as [182]
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“However, human liver transplant studies show that systemic ApoE does not enter into the central nervous system due to the blood brain barrier and knockout of hepatic ApoE does not have an effect on Aβ pathology in the APP/PS1-21 mouse model of Aβ amyloidosis [15, 16].”
From ApoE lipoproteins in the central nervous system under homeostasis and role in Alzheimer’s disease and related disorders (2026) · cites this paper as [16]
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“suggesting that apoE in blood and brain are regulated independently.61,63”
From Plasma levels of apolipoprotein E, APOE genotype, and all-cause and cause-specific mortality in 105 949 individuals from a white general population cohort (2019) · cites this paper as [61]
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“Human liver transplantation studies clearly showed that apoE in the peripheral circulation and in the central nervous system originates from two separate compartments.61”
From Plasma levels of apolipoprotein E, APOE genotype, and all-cause and cause-specific mortality in 105 949 individuals from a white general population cohort (2019) · cites this paper as [61]
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“About 90% of serum apoE is made in the liver ( 10 ) and the remainder is produced by macrophages ( 11 ).”
From Macrophage-derived apoESendai suppresses atherosclerosis while causing lipoprotein glomerulopathy in hyperlipidemic mice (2014) · cites this paper as [10]
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“However, human liver transplant studies show that systemic ApoE does not enter into the central nervous system due to the blood brain barrier and knockout of hepatic ApoE does not have an effect on Aβ pathology in the APP/PS1-21 mouse model of Aβ amyloidosis [15, 16].”
From ApoE lipoproteins in the central nervous system under homeostasis and role in Alzheimer’s disease and related disorders (2026) · cites this paper as [16]
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Metadata
- Authors
- Linton, M. F., Gish, R., Hubl, S. T., Bütler, E., Esquivel, C., Bry, W. I., Boyles, J. K., Wardell, M. R., & Young, S. G.
- Affiliations
- University of California, San Francisco (US)
- Gladstone Institutes (US)
- Venue
- Journal of Clinical Investigation
- Published
- 1991-07-01
- Volume
- 88
- Issue
- 1
- Pages
- 270-281
- ISSN
- 0021-9738 (ISSN-L)
- OpenAlex
- W2115309238
- Cited by
- 367
- References
- 60
- Citations by year
- 2026: 8 · 2025: 20 · 2024: 12 · 2023: 20 · 2022: 18 · 2021: 11 · 2020: 25 · 2019: 13 · 2018: 4 · 2017: 9 · 2016: 8 · 2015: 11 · 2014: 13 · 2013: 10 · 2012: 11
- FWCI
- 4.40
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- PubMed (publishedVersion)
- Funders
- American Heart Association
- National Institutes of Health
- National Heart, Lung, and Blood Institute (HL-41633, P01HL041633, HL 01672)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipid metabolism and disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Cholesterol and Lipid Metabolism
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipoproteins and Cardiovascular Health
- Keywords
- apolipoprotein E, apolipoprotein B, apolipoprotein B-48, apolipoprotein B-100, liver transplantation, chylomicrons, VLDL, lipoprotein metabolism
- MeSH terms
- Adult, Apolipoproteins B, Apolipoproteins E, Chylomicrons, Glycosylation, Humans, Immunohistochemistry, Lipoproteins, VLDL, Middle Aged, Phenotype, Liver Transplantation
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