title: Modulation by DLST of the genetic risk of Alzheimer's disease in a very elderly population.
abstract: The mitochondrial alpha-ketoglutarate dehydrogenase complex (KGDHC) is deficient in Alzheimer's disease (AD). The DLST gene encodes the core, dihydrolipoyl succinyltransferase (DLST) component of KGDHC, and recent reports indicate an association between polymorphisms of DLST and AD in both white and Japanese patients. We therefore examined the relationship between AD and the DLST and apolipoprotein E (APOE) genes in elderly (89 +/- 7 years) AD patients, in whom the epsilon4 allele of APOE (APOE4) is a weak risk factor for AD. Polymorphisms of DLST (A19,117G and T19,183C), shown to be of interest in previous studies, were analyzed by restriction fragment length polymorphism analysis after polymerase chain reaction amplification. In a series of 429 white subjects from two Jewish nursing homes, an association of APOE4 with AD was found only in patients homozygous for the G,C allele of DLST. Similar relationships occurred in the "very elderly" (> or =85 years, n = 302) subgroup of this series, and also in an autopsy series (n = 225) that included white subjects from the Jewish nursing homes as well as other white subjects. These findings suggest a relationship between APOE4 and a DLST locus in the pathogenesis of AD in very elderly subjects.
authors.affiliation: Burke Medical Research Institute, White Plains, NY 10605, USA.
authors.forename: K F
authors.initials: KF
authors.lastname: Sheu
authors.forename: A M
authors.initials: AM
authors.lastname: Brown
authors.forename: V
authors.initials: V
authors.lastname: Haroutunian
authors.forename: B S
authors.initials: BS
authors.lastname: Kristal
authors.forename: H
authors.initials: H
authors.lastname: Thaler
authors.forename: M
authors.initials: M
authors.lastname: Lesser
authors.forename: R N
authors.initials: RN
authors.lastname: Kalaria
authors.forename: N R
authors.initials: NR
authors.lastname: Relkin
authors.forename: R C
authors.initials: RC
authors.lastname: Mohs
authors.forename: L
authors.initials: L
authors.lastname: Lilius
authors.forename: L
authors.initials: L
authors.lastname: Lannfelt
authors.forename: J P
authors.initials: JP
authors.lastname: Blass
mesh_terms: D000217:Acyltransferases / Q000235:genetics*; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D000544:Alzheimer Disease / Q000453:epidemiology* / Q000235:genetics*; D053327:Apolipoprotein E4; D001057:Apolipoproteins E / Q000235:genetics; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D011110:Polymorphism, Genetic; D015183:Restriction Mapping; D012307:Risk Factors
chemical_list: D053327:Apolipoprotein E4; D001057:Apolipoproteins E; D000217:Acyltransferases; C021515:dihydrolipoamide succinyltransferase