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Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: OBJECTIVE, METHODS, RESULTS. Meshes: Aged, Alzheimer Disease, Apolipoprotein A-V, Apolipoproteins, Apolipoproteins A, Apolipoproteins E, Brain, Brain Chemistry, Cholesterol, Cholesterol 24-Hydroxylase, Cross-Cultural Comparison, European Continental Ancestry Group, Female, Genetic Heterogeneity, Genetic Predisposition to Disease, Genetic Testing, Greece, Humans, Hydroxycholesterols, Male, Multigene Family, Polymorphism, Single Nucleotide, Receptors, LDL, Receptors, Oxidized LDL, Risk Factors, Scavenger Receptors, Class E, Steroid Hydroxylases, Switzerland.
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Does a cluster of cholesterol-related genes confer susceptibility for Alzheimer 's disease? Context: 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. 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. 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.
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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. Final Decision: yes