Modulation by DLST of the genetic risk of Alzheimer's disease in a very elderly population

The mitochondrial α‐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 an...

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Bibliographic Details
Published in:Annals of neurology 1999-01, Vol.45 (1), p.48-53
Main Authors: Sheu, Kwan-Fu Rex, Brown, Abraham M., Haroutunian, Vahram, Kristal, Bruce S., Thaler, Howard, Lesser, Martin, Kalaria, Rajesh N., Relkin, Norman R., Mohs, Richard C., Lilius, Lena, Lannfelt, Lars, Blass, John P.
Format: Article
Language:English
Subjects:
Acyltransferases - genetics
Age Factors
Aged
Aged, 80 and over
Alleles
Alzheimer Disease - epidemiology
Alzheimer Disease - genetics
Apolipoprotein E4
Apolipoproteins E - genetics
Biological and medical sciences
Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases
Female
Genotype
Humans
Male
Medical sciences
Neurology
Polymorphism, Genetic
Restriction Mapping
Risk Factors
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Summary:The mitochondrial α‐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 ε4 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” (≥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. Ann Neurol 1999;45:48–53
ISSN:0364-5134
1531-8249
DOI:10.1002/1531-8249(199901)45:1<48::AID-ART9>3.0.CO;2-V