title: Polymorphism in ABCA1 influences CSF 24S-hydroxycholesterol levels but is not a major risk factor of Alzheimer's disease.
abstract: The ATP-binding cassette transporter A1 (ABCA1) mediates reverse cholesterol transport, polymorphisms have been shown to influence the levels of cholesterol and of HDL and the risk of coronary artery disease. Since altered cholesterol metabolism is also involved in Alzheimer's disease (AD), the effects of two ABCA1 polymorphisms (G-395C promoter polymorphism (rs 2246293) and exonic R219K) on the risk of AD in 241 AD patients and 294 non-demented controls, and on CSF cholesterol and 24S-hydroxycholesterol in 74 AD patients and 42 non-demented controls were investigated. None of the investigated ABCA1 polymorphisms influenced the risk of AD. However, the ABCA1 G-395C polymorphism influenced CSF levels of 24S-hydroxycholesterol, but not of cholesterol, whereas the R219K influenced neither CSF levels of 24S-hydroxycholesterol nor cholesterol. Our data support the observation that ABCA1 polymorphisms influence cholesterol metabolism of the brain, but might not act as a major risk factor in AD.
authors.affiliation: Department of Psychiatry, University of Bonn, 53105 Bonn, Germany. heike.koelsch@ukb.uni-bonn.de
authors.forename: Heike
authors.initials: H
authors.lastname: Kölsch
authors.forename: Dieter
authors.initials: D
authors.lastname: Lütjohann
authors.forename: Frank
authors.initials: F
authors.lastname: Jessen
authors.forename: Klaus
authors.initials: K
authors.lastname: Von Bergmann
authors.forename: Sandra
authors.initials: S
authors.lastname: Schmitz
authors.forename: Horst
authors.initials: H
authors.lastname: Urbach
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Maier
authors.forename: Reinhard
authors.initials: R
authors.lastname: Heun
mesh_terms: D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid / Q000235:genetics*; D002784:Cholesterol / Q000134:cerebrospinal fluid; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D006888:Hydroxycholesterols / Q000134:cerebrospinal fluid*; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011110:Polymorphism, Genetic; D012307:Risk Factors
chemical_list: C577836:ABCA1 protein, human; D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters; D006888:Hydroxycholesterols; C044563:24-hydroxycholesterol; D002784:Cholesterol