The deficiency in a mitochondrial aldehyde dehydrogenase as a risk factor of Alzheimer’s disease：Its molecular mechanism and a model animal

Ikuroh Ohsawa, Shigeo Ohta

　　Department of Biochemistry and Cell Biology, Institute of Development and Aging Sciences, Graduate School of Medicine, Nippon Medical School

　　Mitochondrial aldehyde dehydrogenase 2 (ALDH2) is believed to play a major role in acetaldehyde detoxification in the ethanol metabolism.　Our molecular epidemiologic analysis has shown association of Alzheimer’s disease (AD) with a mutant allele of the ALDH2 gene (ALDH2^*2).　We here discuss the molecular mechanism underlying the promotion of AD onset by the ALDH2 deficiency.　ALDH2 is involved in the defense against oxidative stress by detoxifying aldehydes, such as 4-hydroxyl-2-nonenal, that are derived from lipid-peroxides.　ALDH2 deficient transgenic mice were constructed by introducing a mouse version of ALDH2^*2 and found to exhibit neurodegeneration and dementia in an age dependent manner.

Address correspondence to Dr. Ikuroh Ohsawa, Department of Biochemistry and Cell Biology, Institute of Development and Aging Sciences, Graduate School of Medicine, Nippon Medical School (1-396, Kosugi-cho, Nakahara-ku, Kawasaki 211-8533, Japan)