Individuals who often drink alcohol and then experience facial redness following consumption (aka “Asian glow”) may be more susceptible to Alzheimer’s disease, a new study suggests.
A research team at the Stanford University School of Medicine has found that the redness, caused by a mutation in mitochondrial aldehyde dehydrogenase 2 (ALDH2), increases damage in cells in mice and patients with Alzheimer’s disease.
ALDH2 plays a key role in removing toxic aldehydes (product of alcohol metabolism) in the body and its deficient variant, called the ALDH2*2 genotype, has a significantly lower ability to remove the toxic byproduct.
Overall, about 8% of the world’s population, (560 million people) possess this mutation, according to Daria Mochly-Rosen, Ph.D., professor of chemical and systems biology.
Mochly-Rosen, the senior author of the study, pointed out that a better understanding of the relationship between alcohol and genes linked to Alzheimer’s disease would be significant. Millions of people may be unknowingly endangering their health by their regular alcohol consumption.
“Our data suggest that alcohol and Alzheimer’s disease-prone genes may put humans at greater risk of Alzheimer’s onset and progression,” Mochly-Rosen was quoted as saying. “This is based on our patient-derived cell studies and our animal studies, so an epidemiological study in humans should be carried out in the future.”
In the current study, published in Acta Neuropathologica Communications
on Thursday, the scientists first examined cell cultures made using cells from 20 patients with Alzheimer’s disease. It was then found that the ALDH2*2 cells had more free radicals and more 4-HNE, another toxic chemical, compared to normal cells.
The study noted that introducing alcohol to cells with either ALDH2 or ALDH2*2 taken from patients with Alzheimer’s disease resulted in an increase in free radicals, with the ALDH2*2 cells showing greater effect.
“Free radicals are formed when we have a fever, when we have chronic diseases, when we are stressed; free radicals are formed under many kinds of pathological stimuli. These free radicals form toxic aldehydes, and the job of ALDH2 is to remove these toxic chemicals,” Mochly-Rosen said.
“Once these aldehydes accumulate, the first organelles that they damage are the organelles that contain the enzyme that is supposed to get rid of them: the mitochondria.”
Furthering the study, the research team injected mice carrying ALDH2*2 with alcohol each day for 11 weeks to simulate chronic alcohol use.
Findings showed that mice with the ALDH2*2 gene produced more free radicals than normal mice after the alcohol injection. This eventually resulted in reduced mitochondrial activity, increased free radical formation and death of neurons in the case of Alzheimer’s disease.
Compared to the normal mice, the ALDH2*2 mice also exhibited an increase in neuroinflammatory signs. While neuroinflammation (inflammation of the nervous system) is normally caused by injury, infection and old age, recent studies have found that chronic neuroinflammation worsens the progression of neurodegenerative diseases, such as Alzheimer’s disease.
Treatment with Alda-1 reduced the accumulation of these neuroinflammatory proteins in mice. Back in 2008, Mochly-Rosen and her research team discovered that Alda-1 is able to restore ALDH2*2 to normal while also activating the normal enzyme.
While there has been previous research that suggested a link between facial flushing and Alzheimer’s disease, some of them failed to establish an association.
Mochly-Rosen admitted that further studies are required to fully establish whether alcohol drinkers who have the ALDH2*2 mutation develop Alzheimer’s disease at a higher-than-average rate. She noted that such studies could help determine whether reduced alcohol consumption and treatment with compounds might help reduce the progression and effects of Alzheimer’s disease in patients.