The DOI matches its Crossref record, with a small difference in title or year.
Focus on Alzheimer's Disease and Related Disorders: A Cluster of Cholesterol-Related Genes Confers Susceptibility for Alzheimer's Disease
Abstract
Objective Polygenic diseases are related to the complex interplay of genetic variations. We evaluated whether clusters of cholesterol- and lipid-related genetic variations are associated with Alzheimer's disease. Method We analyzed 12 cholesterol-related single nucleotide polymorphisms and 48 control polymorphisms in 545 study participants (Alzheimer's disease group N = 284; control group N = 261). Diagnoses of Alzheimer's disease were made according to the NINCDS-ADRDA criteria. Multi-locus genetic association analysis was done with the set-association method. Dates of data collection were from January 2000 to December 2003. Results We identified a cluster of polymorphisms in APOE, SOAT1, APOE 5'-untranslated region, OLR1, CYP46A1, LPL, LIPA, and APOA4 conferring significant (p = .0002) susceptibility for Alzheimer's disease. This gene cluster reached a diagnostic accuracy of 74% and correlated significantly (p = .018) with the levels of the brain cholesterol catabolite 24S-hydroxycholesterol in the cerebrospinal fluid. Conclusion Our results establish a novel approach for the identification of disease-related genetic clusters and demonstrate the need for multi-locus methods in the genetics of complex diseases.
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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 [31]
LPL in brain has been implicated in regulation of body weight and energy balance as well as cognition.
“The function of LPL in the brain still remains elusive, but it has been implicated in at least two different functions; the regulation of body weight and energy balance as well as cognition [14,15].”
From Differential effects of angiopoietin-like 4 in brain and muscle on regulation of lipoprotein lipase activity (2015) · cites this paper as [15]
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Lipoprotein Lipase in the Brain and Nervous System
Wang, H., & Eckel, R. H. (2012) · Annual Review of Nutrition · doi:10.1146/annurev-nutr-071811-150703 · Cited by 105
Wexler, E. M., Rosen, E., Lu, D., Osborn, G. E., Martin, E., Raybould, H., & Geschwind, D. H. (2011) · Science Signaling · doi:10.1126/scisignal.2002282 · Cited by 56
Olarte, L., Schupf, N., Lee, J. H., Tang, M.-X., Santana, V., Williamson, J., Maramreddy, P., Tycko, B., & Mayeux, R. (2006) · Archives of Neurology · doi:10.1001/archneur.63.11.1586 · Cited by 42
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
Vienberg, S. G., Kleinridders, A., Suzuki, R., & Kahn, C. R. (2015) · Molecular Metabolism · doi:10.1016/j.molmet.2014.11.003 · Cited by 33
Metadata
- Authors
- Papassotiropoulos, A., Wollmer, M. A., Tsolaki, M., Brunner, F., Molyva, D., Lütjohann, D., Nitsch, R. M., & Hock, C.
- Venue
- The Journal of Clinical Psychiatry
- Publisher
- Physicians Postgraduate Press, Inc
- Published
- 2005-07-15
- Volume
- 66
- Issue
- 07
- Pages
- 940-947
- ISSN
- 0160-6689
- Cited by
- 80
- References
- 0
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