[Roles of mitochondrial dysfunctions in Alzheimer's disease--contribution of deficiency of ALDH 2].
Mitochondrial aldehyde dehydrogenase 2 (ALDH 2) 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 ALDH 2 caused by the dominant-negative mutant allele of the ALDH 2 gene (ALDH 2 * 2). In a comparison of 447 patients with sex, age and region matched non-demented controls, the genotype frequency carrying the ALDH 2 * 2 allele was significantly higher in the patients than in the controls (p = 0.001, Odds ratio 1.6). Logistic regression analysis indicates that carriage of the ALDH 2 * 2 allele is an independent risk for LOAD of the epsilon 4 allele of the apolipoprotein E gene (APOE-epsilon 4) (p = 0.002). Moreover, the odds ratio for LOAD in carriers of the ALDH 2 * 2 allele was almost twice that in non-carriers irrespective of status with regard to the APOE-epsilon 4 allele. Among patients homozygous for the APOE-epsilon 4 allele, age at onset of LOAD was significantly lower in those with than without the ALDH 2 * 2 allele. In addition, dosage of the ALDH 2 * 2 allele significantly affected age at onset of patients homozygous for the APOE-epsilon 4 allele. These results indicate that the ALDH 2 deficiency is a risk for LOAD, synergistically acting with the APOE-epsilon 4 allele.
Ohta
S
S
Institute of Gerontology, Nippon Medical School.
D017668:Age of Onset; D000444:Aldehyde Dehydrogenase / Q000172:deficiency* / Q000235:genetics; D000071396:Aldehyde Dehydrogenase, Mitochondrial; D000483:Alleles; D000544:Alzheimer Disease / Q000209:etiology*; D053327:Apolipoprotein E4; D001057:Apolipoproteins E / Q000235:genetics; D044466:Asian People; D016022:Case-Control Studies; D005838:Genotype; D006801:Humans; D007564:Japan; D008928:Mitochondria / Q000201:enzymology*; D009154:Mutation; D018384:Oxidative Stress; D012306:Risk
D053327:Apolipoprotein E4; D001057:Apolipoproteins E; C096127:ALDH2 protein, human; D000444:Aldehyde Dehydrogenase; D000071396:Aldehyde Dehydrogenase, Mitochondrial