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Deficiency in Mitochondrial Aldehyde Dehydrogenase Increases the Risk for Late-Onset Alzheimer's Disease in the Japanese Population

https://doi.org/10.1006/bbrc.2000.2923Get rights and content

Abstract

Mitochondrial aldehyde dehydrogenase 2 (ALDH2) deficiency is caused by a mutant allele in the Mongoloids. To examine whether genetic constitutions affecting aldehyde metabolism influence the risk for late-onset Alzheimer's disease (LOAD), we performed a case–control study in the Japanese population on the deficiency in ALDH2 caused by the dominant-negative mutant allele of the ALDH2 gene (ALDH2*2). In a comparison of 447 patients with sex, age, and region matched nondemented controls, the genotype frequency carrying the ALDH2*2 allele was significantly higher in the patients than in the controls (48.1% vs 37.4%, P = 0.001). Logistic regression analysis indicates that carriage of the ALDH2*2 allele is an independent risk for LOAD of the ϵ4 allele of the apolipoprotein E gene (APOE-ϵ4) (P = 0.002). Moreover, the odds ratio for LOAD in carriers of the ALDH2*2 allele was almost twice that in noncarriers, irrespective of status with regard to the APOE-ϵ4 allele. Among patients homozygous for the APOE-ϵ4 allele, age at onset of LOAD was significantly lower in those with than without the ALDH2*2 allele. In addition, dosage of the ALDH2*2 allele significantly affected age at onset of patients homozygous for the APOE-ϵ4 allele. These results indicate that the ALDH2 deficiency is a risk for LOAD, synergistically acting with the APOE-ϵ4 allele.

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    To whom correspondence should be addressed at Department of Biochemistry and Cell Biology, Institute of Gerontology, Nippon Medical School, 1-396, Kosugi-cho, Nakahara-ku, Kawasaki City, Kanagawa-ken 211-8533 Japan. Fax: +81 44 733 1877. E-mail: [email protected].

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