ALDH2 Mutation and Alcohol Impact on Alzheimer’s Disease

Published on August 24, 2023

Imagine you have a trusty enzyme in your body called ALDH2 that helps break down alcohol and other harmful substances. But what if this enzyme had a small mutation? Well, in East Asians, about 8% of the population has a common ALDH2 mutation called ALDH2*2. And guess what? This mutation has been linked to a variety of diseases, including Alzheimer’s disease (AD). Researchers have found that when this mutation is present, it can contribute to the onset and progression of AD. Now, let’s talk about alcohol. Some studies have shown that heavy alcohol consumption is associated with an increased risk of developing AD. And interestingly, when mice with the ALDH2*2 mutation were given alcohol, their AD-like symptoms worsened. This suggests that both the ALDH2 mutation and alcohol consumption could play a role in AD. It’s still early days for understanding all the details, but there’s exciting research happening to uncover more about how these factors interact and impact the development of AD. If you’re curious to learn more, check out the full article!

Aldehyde dehydrogenase 2 (ALDH2) is an enzyme found in the mitochondrial matrix that plays a central role in alcohol and aldehyde metabolism. A common ALDH2 polymorphism in East Asians descent (called ALDH2*2 or E504K missense variant, SNP ID: rs671), present in approximately 8% of the world’s population, has been associated with a variety of diseases. Recent meta-analyses support the relationship between this ALDH2 polymorphism and Alzheimer’s disease (AD). And AD-like pathology observed in ALDH2–/– null mice and ALDH2*2 overexpressing transgenic mice indicate that ALDH2 deficiency plays an important role in the pathogenesis of AD. Recently, the worldwide increase in alcohol consumption has drawn attention to the relationship between heavy alcohol consumption and AD. Of potential clinical significance, chronic administration of alcohol in ALDH2*2/*2 knock-in mice exacerbates the pathogenesis of AD-like symptoms. Therefore, ALDH2 polymorphism and alcohol consumption likely play an important role in the onset and progression of AD. Here, we review the data on the relationship between ALDH2 polymorphism, alcohol, and AD, and summarize what is currently known about the role of the common ALDH2 inactivating mutation, ALDH2*2, and alcohol in the onset and progression of AD.

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