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Functional interaction between APOE4 and LDL receptor isoforms in Alzheimer's disease
Open accessAbstract
Background: Multiple genes have been provisionally associated with Alzheimer’s disease, including the coding polymorphisms in exons 8 and 13 in the low density lipoprotein receptor gene (LDLR), situated on chromosome 19p13.2. Methods: The sample groups consisted of 180 AD patients and 141 control spouses. We carried out genotyping of LDLR8 and LDLR13. Results: The LDLR8 GG genotype was common, found in 84% of the unaffected control subjects and 91% of the AD patients in our study. There was a ninefold elevation in risk associated with GG:CC versus A– and T– among APOE4+ subjects when compared with APOE4− subjects (odds ratio 9.3; 95% confidence interval 1.8 to 48.2). With the additional information on LDLR polymorphism, we defined an overall 12 fold elevation in risk for APOE4 in combination with LDLR GG:CC (11.9; 2.8 to 50.0; Fisher’s exact test, p = 0.0002; standard power 0.999), compared with other subjects lacking all three of these polymorphisms. Conclusion: These results imply a functional interaction between ApoE and LDL receptor proteins that determines risk for Alzheimer’s disease.
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Several groups identified a potential contribution of LDLR to AD and investigated potential links, with some apparently opposing results.
“Several groups identified a potential contribution of LDLR to AD and investigated potential links, for example by crossing AD transgenic mice with the LDLR−/− mouse model of hypercholesterolemia to investigate the effects of LDLR deficiency [30]–[40]. Some apparently opposing results were obtained.”
From LDLR Expression and Localization Are Altered in Mouse and Human Cell Culture Models of Alzheimer's Disease (2010) · cites this paper as [33]
The Discussion reports an earlier study finding no association between two LDLR polymorphisms and late-onset AD, while the paper's own results associate an LDLR genotype combination with increased AD risk in APOE4 carriers. This supports investigation of a potential LDLR–AD link and apparently differing findings. The cited paper studies human genotypes, however; it does not report crossing AD transgenic mice with LDLR-deficient mice, the example included in the cited sentence. (LLM, conf=0.84)
Experimental — accuracy not yet measuredA functional interaction between apoE and LDLR is a potential mechanism to explain the apoE isoform-dependent disease risks associated with both CVD and AD.
“Together with epidemiological studies (Cheng et al., 2005, Gopalraj et al., 2005, Retz et al., 2001, Vermissen et al., 2011, Zou et al., 2008), these data point toward a functional interaction between apoE and LDLR as a potential mechanism to explain the apoE isoform-dependent disease risks associated with both CVD and AD.”
From Apolipoprotein E–low density lipoprotein receptor interaction affects spatial memory retention and brain ApoE levels in an isoform-dependent manner (2014) · cites this paper as Cheng et al., 2005
The Abstract concludes that the results imply a functional interaction between ApoE and LDL receptor proteins affecting Alzheimer’s disease (AD) risk, and the Discussion proposes that particular combinations may modify that risk. The paper discusses cholesterol metabolism but does not connect the interaction to cardiovascular disease (CVD) risk, so it supports the AD portion, not the claim about both diseases. (LLM, conf=0.88)
Experimental — accuracy not yet measuredSeveral studies reported that a few single-nucleotide polymorphisms (SNPs) in LDLR gene are associated with the risk of developing AD in case-control studies.
“Several studies reported that a few single-nucleotide polymorphisms (SNPs) in LDLR gene are associated with the risk of developing AD in case-control studies (Cheng et al., 2005; Gopalraj et al., 2005; Retz et al., 2001).”
From Overexpression of Low-Density Lipoprotein Receptor in the Brain Markedly Inhibits Amyloid Deposition and Increases Extracellular Aβ Clearance (2009) · cites this paper as Cheng et al., 2005
Polymorphisms in LDLR exon 8 and exon 13 present in conjunction with an ε4 allele increase AD risk.
“Furthermore, studies by Retz et al. (2001) and Cheng et al. (2005) demonstrated an increase in AD risk when polymorphisms in LDLR exon 8 and exon 13 were present in conjunction with an ε4 allele.”
From Apolipoprotein E–low density lipoprotein receptor interaction affects spatial memory retention and brain ApoE levels in an isoform-dependent manner (2014) · cites this paper as Cheng et al. (2005)
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Protective effect of apolipoprotein E type 2 allele for late onset Alzheimer disease
Corder, E. H., Saunders, A. M., Risch, N. J., Strittmatter, W. J., Schmechel, D. E., Gaskell, P. C., Rimmler, J. B., Locke, P. A., Conneally, P. M., Schmader, K. E., et al. (1994) · Nature Genetics · doi:10.1038/ng0694-180 · Cited by 1,920
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Research works printed but not linked: 19
- 10.1126/science.8346443 · DOI · Paper page
- 10.1001/jama.1997.03550160069041 · DOI · Paper page
- 10.1126/science.3283935 · DOI · Paper page
- 10.1161/01.ATV.0000094963.07902.FB · DOI · Paper page
- 2004, J Lipid Res, 45, 403, 10.1194/jlr.R300017-JLR200 · DOI
- 10.1002/humu.1380010602 · DOI · Paper page
- 2000, Biochim Biophys Acta, 1529, 287, 10.1016/S1388-1981(00)00155-4 · DOI
- 10.1097/00041444-200109000-00002 · DOI · Paper page
- 1995, Clin Genet, 47, 68, 10.1111/j.1399-0004.1995.tb03926.x · DOI
- 1989, S Afr Med J, 76, 402
- 1994, Arterioscler Thromb, 14, 663, 10.1161/01.ATV.14.5.663 · DOI
- 10.1136/jmg.40.6.424 · DOI
- 10.1159/000053076 · DOI
- 10.1093/hmg/ddh119 · DOI
- 10.1212/WNL.45.6.1092 · DOI
- 10.1212/WNL.34.7.939 · DOI · Paper page
- 2003, Genetics, 164, 1567, 10.1093/genetics/164.4.1567 · DOI
- 10.1023/A:1022409617539 · DOI
- 10.1086/383282 · DOI
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Fotuhi, M., Hachinski, V., & Whitehouse, P. J. (2009) · Nature Reviews Neurology · doi:10.1038/nrneurol.2009.175 · Cited by 291
Kim, J., Castellano, J. M., Jiang, H., Basak, J. M., Parsadanian, M., Pham, V., Mason, S. M., Paul, S. M., & Holtzman, D. M. (2009) · Neuron · doi:10.1016/j.neuron.2009.11.013 · Cited by 274
Johnson, L. A., Olsen, R. H. J., Merkens, L. S., DeBarber, A., Steiner, R. D., Sullivan, P. M., Maeda, N., & Raber, J. (2014) · Neurobiology of Disease · doi:10.1016/j.nbd.2013.12.016 · Cited by 107
Lack of LDL receptor aggravates learning deficits and amyloid deposits in Alzheimer transgenic mice
Cao, D., Fukuchi, K.-I., Wan, H., Kim, H., & Li, L. (2006) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2005.09.011 · Cited by 106
Abisambra, J. F., Fiorelli, T., Padmanabhan, J., Neame, P., Wefes, I., & Potter, H. (2010) · PLoS ONE · doi:10.1371/journal.pone.0008556 · Cited by 42
Metadata
- Authors
- Cheng, D., Huang, R., Lanham, I. S., Cathcart, H. M., Howard, M., Corder, E. H., & Poduslo, S. E.
- Affiliations
- Augusta University (US)
- Duke University (US)
- Corresponding author
- Poduslo, S E
- Venue
- Journal of Medical Genetics
- Publisher
- BMJ
- Published
- 2005-02
- Volume
- 42
- Issue
- 2
- Pages
- 129-131
- ISSN
- 0022-2593 (ISSN-L)
- 1468-6244
- PMC
- PMC1735987
- OpenAlex
- W2026895373
- Cited by
- 33
- References
- 1
- Citations by year
- 2026: 1 · 2022: 1 · 2021: 2 · 2020: 1 · 2019: 2 · 2018: 1 · 2014: 2 · 2012: 1
- FWCI
- 2.61
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Medical Genetics (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute on Aging (U24 AG21886, U24AG021886)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipoproteins and Cardiovascular Health
- Keywords
- Alzheimer's disease, APOE ε4, LDL receptor, genetic risk, gene-gene interaction, lipid metabolism
- MeSH terms
- Aged, Aged, 80 and over, Alzheimer Disease, Apolipoproteins E, Female, Genotype, Humans, Male, Middle Aged, Polymorphism, Genetic, Receptors, LDL, Genetic Predisposition to Disease, Protein Isoforms, Apolipoprotein E4
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