Novel Large Apolipoprotein E‐Containing Lipoproteins of Density 1.006–1.060 g/ml in Human Cerebrospinal Fluid

Guyton, John R.; Miller, Sara; Martin, Margaret E.; Khan, Waris; Roses, Allen D.; Strittmatter, Warren J.

doi:10.1046/j.1471-4159.1998.70031235.x

Cited by 43 publications

(28 citation statements)

References 19 publications

(25 reference statements)

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“…It is expressed in virtually all cells and tissues at variable levels, which our findings in TaqCell plates confirm. The LDL-r is widely expressed in brain and, as apoB100 and LDL are absent from cerebrospinal fluid [31], it appears that their role in lipid transport and cholesterol homeostasis is fulfilled by apoE [17,31].…”

Section: Discussionmentioning

confidence: 99%

Quantification of apolipoprotein E receptors in human brain-derived cell lines by real-time polymerase chain reaction

Thilakawardhana

Everett

Murdock

et al. 2005

Neurobiology of Aging

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Apolipoprotein (apo) E4 is a risk factor for Alzheimer's disease, compared to wild-type apoE3. The mechanism(s) is unknown. One possibility, demonstrated in peripheral tissue cell lines, is that apoE stimulates nitric oxide synthase (NOS) via a receptor-dependent signalling pathway and that apoE4 generates inappropriate amounts of NO compared to apoE3. Prior to biochemical investigations, we have quantified the expression of several candidate receptor genes, including low-density lipoprotein (LDL)-receptor family members and scavenger receptor class B, types I and II (SR-BI/II), as well as the three NOS isoenzymes and protein kinase B (Akt), in 38 human cell lines, of which 12 derive from brain. Expression of apoE receptor 2 (apoER2), a known signalling receptor in brain, was readily detected in SH-SY-5Yand CCF-STTG1 cells, common models of neurons and astrocytes, respectively, and was highest in H4 neuroglioma and IMR-32 neuroblastoma cells. Transcripts of the other lipoprotein receptors were widely, but variably, distributed across the different cell types. Of particular note was the predominant expression of SR-BII over SR-BI in many of the brainderived cells. As the C-terminus of SR-BII, like apoER2, contains potential SH3 signalling motifs, we suggest that in brain SR-BII functions as a signal transducer receptor.

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Section: Discussionmentioning

confidence: 99%

Quantification of apolipoprotein E receptors in human brain-derived cell lines by real-time polymerase chain reaction

Thilakawardhana

Everett

Murdock

et al. 2005

Neurobiology of Aging

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“…The distribution of lipoprotein classes and their composition differ markedly between sera and cerebrospinal fluid (CSF). Moreover, the effects of the APOE genotype on the distribution and metabolism of CSF lipoprotein classes are not completely characterized (27)(28)(29)(30). Therefore, to extend our findings to apoptosis in neurons, lipoproteins from the CSF need to be examined.…”

Section: Discussionmentioning

confidence: 99%

ApoE genotype-specific inhibition of apoptosis

DeKroon

Mihovilovic

Goodger

et al. 2003

Journal of Lipid Research

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Endothelial cell apoptosis can be initiated by withdrawing growth factors or serum, and is inhibited by HDL. Our results show that the total lipoprotein population from apolipoprotein E 4/4 (APOE4/4) sera is less anti-apoptotic than total lipoproteins from other APOE genotypes, as measured by caspase 3/7 activity. Moreover, APOE4/4 VLDL antagonizes the antiapoptotic activity of HDL by a mechanism requiring binding of apoE4 on VLDL particles to an LDL family receptor. This ability of APOE4/4 VLDL to inhibit the antiapoptotic effects of HDL presents a potential mechanism by which the expression of several diseases, including atherosclerosis, is enhanced by the APOE4 genotype.

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“…43 Apolipoproteins and their receptors appear to play an important role in the metabolism of cholesterol in the brain and in the outcome of neuronal injury. 44,45 In addition to facilitating the absorption of the intrinsic factor-vitamin B 12 complex, cubilin is a high-affinity apolipoprotein A-I receptor that facilitates the endocytosis of high-density lipoprotein (HDL) holoparticles and their subsequent transport to endosomes/lysosomes where they are digested. 46,47 This endocytic process resembles that for low-density lipoproteins (LDL) and appears to involve the participation of the co-receptor megalin, a member of the LDL receptor family.…”

Section: Discussionmentioning

confidence: 99%

D10S1423 identifies a susceptibility locus for Alzheimer's disease in a prospective, longitudinal, double-blind study of asymptomatic individuals

2001

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Typical, later-onset forms of Alzheimer's disease (AD) appear to be influenced by multiple susceptibility loci, combinations of which contribute to the development of this disorder. We previously reported the results of a systematic survey of the human genome for the identification of highly informative DNA polymorphisms (SSTRPs) that target new AD risk genes. In addition to the APOE locus, our survey detected five new candidate susceptibility loci for AD, including D10S1423. An association of the D10S1423 234-bp allele with AD has been reported in three independent samples of AD cases and controls (Boston, Pittsburgh, Bonn). Data from our case-control studies suggest a strong synergistic interaction between the D10S1423 234-bp and APOE E4 risk alleles (234-bp carrier: OR = 2.5, 95% CI = 1.4-4.5; E4 carrier: OR = 8.3, 95% CI = 4.3-15.8; both alleles: OR = 23.1, 95% CI = 5.3-99.5). This report describes the prospective, longitudinal, double-blind assessment of the age-specific risk of AD encountered by 325 asymptomatic first-degree relatives of AD probands who carried the D10S1423 234-bp allele, the APOE E4 allele, or both, after 11.5 years of systematic follow-up. A total of 18 incident cases of AD were detected during the first 3379 subject-years of this longitudinal study. The effects of carrying either or both of the D10S1423 234-bp and APOE E4 alleles on the age-specific risk of developing AD were determined using Kaplan-Meier survival analysis. The age-specific risk of developing AD was the greatest for individuals who carried both alleles (Mantel-Cox statistic = 20.12, df = 3, P = 0.0002; Breslow statistic = 13.36, df = 3, P = 0.004). Cox proportional hazards models were developed to estimate the risk ratios for each genotype, controlling for the potential effects of age at recruitment, sex, and years of education. In the resulting best fitting model, only individuals who carried both risk alleles exhibited a risk ratio that differed significantly from 1 (risk ratio = 16.2, P = 0.008, 95% CI = 2.1-128.3). After controlling for these genotypes, female gender was also significantly associated with increased risk of developing AD (risk ratio = 5.1, P = 0.02, 95% CI = 1.2-21.1). Neither age at recruitment nor years of education made significant contributions to the model. Molecular Psychiatry (2001) 6, 413-419.

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Novel Large Apolipoprotein E‐Containing Lipoproteins of Density 1.006–1.060 g/ml in Human Cerebrospinal Fluid

Cited by 43 publications

References 19 publications

Quantification of apolipoprotein E receptors in human brain-derived cell lines by real-time polymerase chain reaction

Quantification of apolipoprotein E receptors in human brain-derived cell lines by real-time polymerase chain reaction

ApoE genotype-specific inhibition of apoptosis

D10S1423 identifies a susceptibility locus for Alzheimer's disease in a prospective, longitudinal, double-blind study of asymptomatic individuals

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