In a new study, researchers found that a common mutation in a key enzyme involved in alcohol metabolism increases damage in cells from individuals with Alzheimer’s disease.
This mutation in aldehyde dehydrogenase 2, or ALDH2, is linked to facial redness following alcohol drinking.
The research was conducted by a team at the Stanford University School of Medicine.
According to the team, the mutation causes the activity of the enzyme to be greatly reduced, resulting in the buildup of acetaldehyde, a toxic product of alcohol metabolism.
The body responds to the presence of the toxin with skin flushing and inflammation.
The mutation is prevalent in the East Asian population. The flushing response to alcohol among people who carry the mutation is sometimes called “Asian glow.”
The mutation occurs in about 560 million people or about 8% of the world’s population.
Previous studies in East Asian populations have previously suggested a link between the mutation in ALDH2 that causes facial flushing and Alzheimer’s disease.
However, there have also been other studies that didn’t find an association.
To further examine a possible role for ALDH2, the team examined cells from 20 patients with Alzheimer’s disease.
They found adding alcohol to cells with either ALDH2 derived from patients with Alzheimer’s disease led to an increase in free radicals.
According to the team, free radicals are formed when people have a fever, when they have chronic diseases when they are stressed; free radicals are formed under many kinds of pathological stimuli.
These free radicals form toxic aldehydes. Once these aldehydes accumulate, they damage the organelles that contain the enzyme that is supposed to get rid of them: the mitochondria.
This vicious cycle ultimately leads to reduced mitochondrial activity, increased free radical formation by the damaged mitochondria and, in the case of Alzheimer’s disease, to death of neurons.
The findings suggest that alcohol and Alzheimer’s disease-prone genes may put humans at greater risk of Alzheimer’s onset and progression.
The study point to a previously undiscovered role of alcohol and ALDH2 in Alzheimer’s disease.
Future work is needed in large studies of humans to see whether alcohol drinkers who have the ALDH2 mutation develop Alzheimer’s disease at a higher-than-average rate.
The lead author of the study is Daria Mochly-Rosen, Ph.D., a professor of chemical and systems biology.
The study is published in Acta Neuropathologica Communications.
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